Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• Human Amylin in the Presence of SARS-COV-2 Protein Fragments -
  Covid-19 can lead to the onset of type-II diabetes which is associated with aggregation of islet amyloid polypeptides, also called amylin. Using molecular dynamics simulations, we investigate how the equilibrium, between amylin monomers in its functional form and fibrils associated with diabetes, is altered in presence of SARS-COV-2 protein fragments. For this purpose, we study the interaction between the fragment SFYVYSRVK of the Envelope protein or the fragment FKNIDGYFKI of the Spike protein with the monomer and two amylin fibril models. Our results are compared with earlier work studying such interactions for two different proteins.
  🖺 Full Text HTML: Human Amylin in the Presence of SARS-COV-2 Protein Fragments
• A dual diffusion model enables 3D binding bioactive molecule generation and lead optimization given target pockets -
  Structure-based generative chemistry aims to explore much bigger chemical space to design a ligand with high binding affinity to the target proteins; it is a critical step in de novo computer-aided drug discovery. Traditional in silico methods suffer from calculation inefficiency and the performances of existing machine learning methods could be bottlenecked by the auto-regressive sampling strategy. To address these concerns, we herein have developed a novel conditional deep generative model, PMDM, for 3D molecule generation fitting specified target proteins. PMDM incorporates a dual equivariant diffusion model framework to leverage the local and global molecular dynamics to generate 3D molecules in a one-shot fashion. By considering the conditioned protein semantic information and spatial information, PMDM is able to generate chemically and conformationally valid molecules which suitably fit pocket holes. We have conducted comprehensive experiments to demonstrate that PMDM can generate drug-like, synthesis-accessible, novel, and high-binding affinity molecules targeting specific proteins, outperforming the state-of-the-art (SOTA) models in terms of multiple evaluation metrics. In addition, we perform chemical space analysis for generated molecules and lead compound optimization for SARS-CoV-2 main protease (Mpro) by only utilizing three atoms as the seed fragment. The experimental results implicate that the structures of generated molecules are rational compared to the reference molecules, and PMDM can generate massive bioactive molecules highly binding to the targeted proteins which are not included in the training set.
  🖺 Full Text HTML: A dual diffusion model enables 3D binding bioactive molecule generation and lead optimization given target pockets
• Machine learning models for predicting severe COVID-19 outcomes in hospitals -

  Objectives The aim of this observational retrospective study is to improve early risk stratification of hospitalized Covid-19 patients by predicting in-hospital mortality, transfer to intensive care unit (ICU) and mechanical ventilation from electronic health record data of the first 24 hours after admission. Methods and Results Our machine learning model predicts in-hospital mortality (AUC=0.918), transfer to ICU (AUC=0.821) and the need for mechanical ventilation (AUC=0.654) from a few laboratory data of the first 24 hours after admission. Models based on dichotomous features indicating whether a laboratory values exceeds or falls below a threshold perform nearly as good as models based on numerical features. Conclusions We devise completely data-driven and interpretable machine-learning models for the prediction of in-hospital mortality, transfer to ICU and mechanical ventilation for hospitalized Covid-19 patients within 24 hours after admission. Numerical values of CRP and blood sugar and dichotomous indicators for increased partial thromboplastin time (PTT) and glutamic oxaloacetic transaminase (GOT) are amongst the best predictors.

  🖺 Full Text HTML: Machine learning models for predicting severe COVID-19 outcomes in hospitals
• Demographic and Viral-Genetic Analyses of COVID-19 Severity in Bahrain Identify Local Risk Factors and a Protective Effect of Polymerase Mutations -

  A multitude of demographic, health, and genetic factors are associated with the risk of developing severe COVID-19 following infection by the SARS-CoV-2. There is a need to perform studies across human societies and to investigate the full spectrum of genetic variation of the virus. Using data from 869 COVID-19 patients in Bahrain between March 2020 and March 2021, we analyzed paired viral sequencing and non-genetic host data to understand host and viral determinants of severe COVID-19. We estimated the effects of demographic variables specific to the Bahrain population and found that the impact of health factors are largely consistent with other populations. To extend beyond the common variants of concern in the Spike protein analyzed by previous studies, we used a viral burden approach and detected a protective effect of low-frequency missense viral mutations in the RNA-dependent RNA polymerase (Pol) gene on disease severity. Our results contribute to the survey of severe COVID-19 in diverse populations and highlight the benefits of studying rare viral mutations.

  🖺 Full Text HTML: Demographic and Viral-Genetic Analyses of COVID-19 Severity in Bahrain Identify Local Risk Factors and a Protective Effect of Polymerase Mutations
• Long-term changes in human mobility responses to COVID-19-related information in Japan -

  How human behaviour has changed over the long term in response to COVID-19-related information, such as the number of COVID-19-infected cases and non-pharmaceutical interventions (NPIs), is under-researched. It is also unclear how the increasing vaccination rates have affected human mobility. We estimate human mobility responses to such COVID-19-related information via the interactive effects model, which controls unobservable human mobility factors, using publicly available daily data on 9human mobility for retail and recreation9 and 9residential spent time9 in each Japanese prefecture. The results show that Japanese citizens were generally fearful of an unknown virus in the first wave of infection; however, they gradually habituated themselves to similar infection information in the subsequent waves. Nevertheless, the level of habituation decreased in view of information regarding new variants that differed from the previous ones. In contrast, as for NPIs, it is more plausible to consider human mobility responses to varying requests rather than habituation. We also find that rapid vaccination promotion motivates people to go out. Furthermore, we are the first to identify spatial interaction of infection information and heterogeneous responses during increasing and decreasing phases of infection. The long-term analysis is crucial for evidence-based policymaking during the long-term pandemic and future pandemics.

  🖺 Full Text HTML: Long-term changes in human mobility responses to COVID-19-related information in Japan
• Optimality of Maximal-Effort Vaccination -

  It is widely acknowledged that vaccinating at maximal effort in the face of an ongoing epidemic is the best strategy to minimise infections and deaths from the disease. Despite this, no one has proved that this is guaranteed to be true if the disease follows multi-group SIR (Susceptible-Infected-Recovered) dynamics. This paper provides a novel proof of this principle for the existing SIR framework, showing that the total number of deaths or infections from an epidemic is decreasing in vaccination effort. Furthermore, it presents a novel model for vaccination which assumes that vaccines are distributed randomly to the unvaccinated population and suggests, using COVID-19 data, that this more accurately captures vaccination dynamics than the model commonly found in the literature. However, as the novel model provides a strictly larger set of possible vaccination policies, the results presented in this paper hold for both models.

  🖺 Full Text HTML: Optimality of Maximal-Effort Vaccination
• Could Attitudes Toward COVID-19 in Spain Render Men More Vulnerable Than Women? -
  The COVID-1 pandemic affects the whole world. Spain is 3rd in the world and 2nd in Europe with largest number of diagnosed cases. Spanish citizens’ attitudes are important in controlling the pandemic. This research assessed key attitudes of the Spanish people toward COVID-19. One study (n =64) was conducted in a shopping center in Madrid and another (n= 640) online. The results of both studies suggest that women in Spain have a ‘more responsible’ attitude toward the COVID-19 than men. Young adults (18-25 years) appear to perceive less threatening the epidemic than older adults. Spanish people’s personal concern about COVID-19 is less than their perceived social alarm about it. Compliance is the strongest predictor of the approval to stay at home, which is the highest rated preventive measure by the Spanish people. These results might help policy makers in targeting public attitudes which could play an important role in the exponentially rising cases of COVID-19.
  🖺 Full Text HTML: Could Attitudes Toward COVID-19 in Spain Render Men More Vulnerable Than Women?
• Unrealistic optimism and HEXACO traits as predictors of risk perception and compliance with COVID-19 preventive measures during the first wave of pandemic -
  The aims of this study were to examine possible differences and factors that contribute to risk perception and compliance with preventive measures at the beginning (T1) and the end (T2) of the first wave of COVID-19 pandemic. The sample consisted of 423 participants (M = 30.29, SD = 14.45; 69% female). Compliance, risk perception and trust in information were significantly higher in T1 than T2. For risk perception, significant predictors in both T1 and T2 were age, Emotionality (HEXACO-PI-R) and Unrealistic Optimism (NLE, Negative Life Events). Trust in information was a significant predictor in T1, while Unrealistic Optimism (Positive Life Events) was a signifi-cant predictor in T2. For compliance, significant predictors in T1 were gender and trust in information while in T2 were Emo-tionality, Extraversion, Conscientiousness (HEXACO-PI-R), NLE and trust in information, for both T1 and T2. In general, findings suggest a much more pronounced role of personality traits in adherence to protective measures at the end than at the beginning of the first wave of the COVID-19 pandemic in Serbia. Also, the results indicate the role of unrealistic opti-mism regarding negative life events in lower compliance with protective measures.
  🖺 Full Text HTML: Unrealistic optimism and HEXACO traits as predictors of risk perception and compliance with COVID-19 preventive measures during the first wave of pandemic
• Migrant healthcare workers during COVID-19: bringing an intersectional health system-related approach into pandemic protection. A German case study -

  Introduction. Migrant healthcare workers played an important role during the COVID-19 pandemic, but data are lacking especially for high-resourced European healthcare systems. This study aims to research migrant healthcare workers through an intersectional health system-related approach, using Germany as a case study. Methods. An intersectional research framework was created and a rapid scoping study performed. Secondary analysis of selected items taken from two COVID-19 surveys was undertaken to compare perceptions of national and foreign-born healthcare workers, using descriptive statistics. Results. Available research is focused on worst-case pandemic scenarios of Brazil and the United Kingdom, highlighting racialised discrimination and higher risks of migrant healthcare workers. The German data did not reveal significant differences between national-born and foreign-born healthcare workers for items related to health status including SARS-CoV-2 infection and vaccination, and perception of infection risk, protective workplace measures, and government measures, but items related to social participation and work conditions with higher infection risk indicate a higher burden of migrant healthcare workers. Conclusions. COVID-19 pandemic policy must include migrant healthcare workers, but simply adding the migration status is not enough. We introduce an intersectional health systems-related approach to understand how pandemic policies create social inequalities and how the protection of migrant healthcare workers may be improved.

  🖺 Full Text HTML: Migrant healthcare workers during COVID-19: bringing an intersectional health system-related approach into pandemic protection. A German case study
• Preoperative SARS-CoV-2 and postoperative outcomes -
  Background Surgical decision making after SARS-CoV-2 infection is influenced by the presence of comorbidity, infection severity, and whether the surgical problem is time-sensitive. Contemporary surgical policy to delay surgery is informed by heterogenous guidance. We aimed to evaluate surgical provision during the COVID-19 pandemic to assess real-world practice and whether deferral remains necessary. Methods Using the OpenSAFELY platform, we adapted the COVIDSurg protocol for a service evaluation of surgical procedures that took place within the English NHS from 17 March 2018 to 17 March 2022. We evaluated whether hospitals within the English NHS adhered to guidance not to operate on patients with seven weeks of an indication of SARS-CoV-2 infection. Additional outcomes were postoperative all-cause mortality (30-day, 6-month), and complications (pulmonary, cardiac, cerebrovascular). The exposure was the interval between the most-recent indication of SARS-CoV-2 infection and subsequent surgery. Findings In any 6-month window, less than 3% of surgical procedures were conducted within seven weeks of an indication of SARS-CoV-2 infection. Mortality for surgery conducted within two weeks of a positive test in the pandemic-with-vaccine era was 1·1%, declining to 0·3% by four weeks. Compared to the COVIDSurg study cohort, outcomes for patient in the English NHS cohort were better during the COVIDSurg data collection period and the pandemic-no-vaccine era. Interpretation Clinicians within the English NHS followed national guidance by operating on very few patients within seven weeks of a positive indication of SARS-CoV-2 infection. Surgical patients’ overall risk following an indication of SARS-CoV-2 infection was and is lower than previously thought. Funding Salaries were funded by National Institute for Health Research (NIHR) Yorkshire and Humber Patient Safety Translational Research Centre. Data assets were funded by UK Research and Innovation. The OpenSAFELY Platform is supported by grants from the Wellcome Trust, Medical Research Council, NIHR, and Health Data Research UK.
  🖺 Full Text HTML: Preoperative SARS-CoV-2 and postoperative outcomes
• High number of SARS-CoV-2 persistent infections uncovered through genetic analysis of samples from a large community-based surveillance study -

  Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections may act as viral reservoirs that could seed future outbreaks 1-5, give rise to highly divergent lineages 6-8, and contribute to cases with post-acute Coronavirus disease 2019 (COVID-19) sequelae (Long Covid) 9,10. However, the population prevalence of persistent infections, their viral load kinetics, and evolutionary dynamics over the course of infections remain largely unknown. We identified 381 infections lasting at least 30 days, of which 54 lasted at least 60 days. These persistently infected individuals had more than 50% higher odds of self-reporting Long Covid compared to the infected controls, and we estimate that 0.09-0.5% of SARS-CoV-2 infections can become persistent and last for at least 60 days. In nearly 70% of the persistent infections we identified, there were long periods during which there were no consensus changes in virus sequences, consistent with prolonged presence of non-replicating virus. Our findings also suggest reinfections with the same major lineage are rare and that many persistent infections are characterised by relapsing viral load dynamics. Furthermore, we found a strong signal for positive selection during persistent infections, with multiple amino acid substitutions in the Spike and ORF1ab genes emerging independently in different individuals, including mutations that are lineage-defining for SARS-CoV-2 variants, at target sites for several monoclonal antibodies, and commonly found in immunocompromised patients 11-14. This work has significant implications for understanding and characterising SARS-CoV-2 infection, epidemiology, and evolution.

  🖺 Full Text HTML: High number of SARS-CoV-2 persistent infections uncovered through genetic analysis of samples from a large community-based surveillance study
• Ethical Issues in Residency Education Related to the COVID-19 Pandemic: A Narrative Inquiry Study -

  Background: Amidst the pandemic, residency programs were faced with new challenges to provide care and educate junior doctors (resident physicians). We sought to understand both the positive and negative experiences of first-year residents during COVID-19, as well as to describe potential ethical issues from their stories. Method: We used narrative inquiry (NI) methodology and applied a semi-structured interview guide that included questions pertaining to ethical principles as well as both positive and negative aspects of the pandemic. Sampling was purposive. Interviews were audio-recorded and transcribed. Three members of the research team coded transcripts in duplicate to elicit themes. A composite story with threads was constructed. Discrepancies were resolved through discussion to attain consensus. Results: Eleven residents participated from Internal Medicine (n=2), Family Medicine (n=2), Ophthalmology (n=1), General Surgery (n=1), Pediatrics (n=1), Diagnostic Radiology (n=1), Public Health (n=1), Psychiatry (n=1), Emergency Medicine (n=1). Resident stories had three common themes in which ethical issues were described: 1) Intersecting healthcare and medical education systems, 2) Public health and the public good, 3) Health systems planning/healthcare delivery. Discussion: The pandemic exacerbated the lack of autonomy experienced by resident physicians. The notion of public health and the public good at times eclipsed individual wellbeing for residents and patients alike. Conclusion: Efforts to understand how resident physicians can be engaged in their own education as well as how they can navigate public health crises with respect to ethical principles could benefit both residency education and healthcare delivery.

  🖺 Full Text HTML: Ethical Issues in Residency Education Related to the COVID-19 Pandemic: A Narrative Inquiry Study
• The Effects of Expectations and Worries on the Experience of COVID-19 Symptoms -

  Introduction: The COVID-19 pandemic has been shown to have profound effects on both mental and physical health. Distress and widespread uncertainty about global events and personal risk are associated with increased worry and negative expectations that impact physical health. Thus, the current pandemic poses a possibility for the experience of nocebo effects. Objective: To evaluate the likelihood of nocebo-induced COVID-19 symptoms in a US sample. Methods: An online study on the mental health impact of COVID-19 asked participants to complete a set of biweekly surveys over a 6-month period between April 2020 and May 2021. We focus on responses from 3,027 individuals who reported never testing positive for COVID-19. We assessed the association between two types of worry and self-reported symptoms of COVID-19. We used multi-level models to examine variations across and within participants over time. We further investigated the effects of pre-existing health conditions and mental health status. Results: There was a positive association between symptoms and both general (b= 2.56, p<0.01) and personal worry (b=2.77, p<0.01). However, worry reported at one timepoint was not specifically associated with symptoms reported two weeks later (p = 0.63, p=0.56). We also found that a greater number of prior clinical comorbidities and greater mental health burden were significant predictors of symptom reporting. Conclusions: These results suggest that increased worries during the COVID-19 pandemic were associated with greater symptoms. Further studies investigating worry and symptoms in populations with confirmed negative COVID-19 tests or isolated populations will be needed to isolate the occurrence of true nocebo effects during the pandemic.

  🖺 Full Text HTML: The Effects of Expectations and Worries on the Experience of COVID-19 Symptoms
• Short- and longer-term all-cause mortality among SARS-CoV-2- infected persons and the pull-forward phenomenon in Qatar -

  Background: Risk of short- and long-term all-cause mortality after a primary SARS-CoV-2 infection is inadequately understood. Methods: A national, matched, retrospective cohort study was conducted in Qatar to assess the risk of all-cause mortality in the national cohort of people infected with SARS-CoV-2 compared with a reference national control cohort of uninfected persons. Associations were estimated using Cox proportional-hazards regression models. Results: Among unvaccinated persons, within 90 days after primary infection, adjusted hazard ratio (aHR) comparing incidence of death in the primary-infection cohort with the infection-naive cohort was 1.19 (95% CI: 1.02-1.39). The aHR was 1.34 (95% CI: 1.11-1.63) in persons more clinically vulnerable to severe COVID-19 and 0.94 (95% CI: 0.72-1.24) in those less clinically vulnerable to severe COVID-19. In subsequent follow-up, the aHR was 0.50 (95% CI: 0.37-0.68). The aHR was 0.41 (95% CI: 0.28-0.58) in months 3-7 after the primary infection and 0.76 (95% CI: 0.46-1.26) in subsequent months. The aHR was 0.37 (95% CI: 0.25-0.54) in persons more clinically vulnerable to severe COVID-19 and 0.77 (95% CI: 0.48-1.24) in those less clinically vulnerable to severe COVID-19. Among vaccinated persons, no evidence was found for differences in incidence of death in the primary-infection versus infection-naive cohorts, even among persons more clinically vulnerable to severe COVID-19. Conclusions: COVID-19 mortality in Qatar appears primarily driven by forward displacement of deaths of individuals with relatively short life expectancy and more clinically vulnerable to severe COVID-19. Vaccination negated the mortality displacement by preventing early deaths.

  🖺 Full Text HTML: Short- and longer-term all-cause mortality among SARS-CoV-2- infected persons and the pull-forward phenomenon in Qatar
• A large-scale machine learning study of sociodemographic factors contributing to COVID-19 severity -

  Understanding sociodemographic factors behind COVID-19 severity relates to significant methodological difficulties, such as differences in testing policies and epidemics phase, as well as a large number of predictors that can potentially contribute to severity. To account for these difficulties, we assemble 115 predictors for more than 3000 US counties and employ a well-defined COVID-19 severity measure derived from epidemiological dynamics modeling. We then use a number of advanced feature selection techniques from machine learning to determine which of these predictors significantly impact the disease severity. We obtain a surprisingly simple result, where only two variables are clearly and robustly selected - population density and proportion of African Americans. Possible causes behind this result are discussed. We argue that the approach may be useful whenever significant determinants of disease progression over diverse geographic regions should be selected from a large number of potentially important factors.

  🖺 Full Text HTML: A large-scale machine learning study of sociodemographic factors contributing to COVID-19 severity

From Clinical Trials

• Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care - Condition:   COVID-19
  Intervention:   Drug: Plitidepsin
  Sponsor:   PharmaMar
  Not yet recruiting

• Evaluation of Corfluvec Vaccine for the Prevention of COVID-19 in Healthy Volunteers - Condition:   COVID-19
  Interventions:   Biological: Corfluvec component 1 low dose;   Biological: Corfluvec component 2 low dose;   Biological: Corfluvec component 1 high dose;   Biological: Corfluvec component 2 high dose;   Biological: Corfluvec low dose;   Biological: Corfluvec high dose;   Biological: Placebo
  Sponsors:   Tatyana Zubkova;   MDP-CRO, LLC;   St. Petersburg State Pavlov Medical University
  Active, not recruiting

• COVID-19 Self-testing Study - Condition:   COVID-19
  Intervention:   Behavioral: SMARTest mobile app for COVID-19 self-testing
  Sponsor:   Columbia University
  Recruiting

• A Study of Efficacy and Safety of Azvudine vs. Nirmatrelvir-Ritonavir in the Treatment of COVID-19 Infection - Condition:   COVID-19
  Interventions:   Drug: Azvudine;   Drug: Nirmatrelvir-Ritonavir
  Sponsors:   Shandong Provincial Hospital;   Central hospital Affiliated to Shandong First Medical University;   The Second Affiliated Hospital of Shandong First Medical University;   The Affiliated Hospital Of Southwest Medical University;   Gansu Provincial Hospital
  Not yet recruiting

• A Chatbot to Enhance COVID-19 Knowledge - Condition:   COVID-19
  Interventions:   Device: chatbot;   Other: Printed educational booklet
  Sponsor:   Sun Yat-sen University
  Not yet recruiting

• Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia - Condition:   COVID-19 Pneumonia
  Intervention:   Radiation: Low-Dose Radiation Therapy
  Sponsors:   Jiangsu Cancer Institute & Hospital;   Nanjing Chest Hospital;   The Affiliated BenQ Hospital of Nanjing Medical University;   Central South University;   Zhongda Hospital
  Not yet recruiting

• Tetrandrine Tablets Used in Hospitalized Adults With COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Tetrandrine
  Sponsor:   Peking University Third Hospital
  Not yet recruiting

• A Phase 2 Study to Evaluate the Efficacy and Safety of QLS1128 Orally in Symptomatic Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: QLS1128;   Drug: Placebo
  Sponsor:   Qilu Pharmaceutical Co., Ltd.
  Recruiting

• Efficacy of Megadose Vitamin C in Severe and Critical Ill COVID-19 Patients. - Conditions:   Vitamin C;   COVID-19 Pneumonia
  Interventions:   Drug: Vitamin C;   Drug: Placebo
  Sponsor:   Zhujiang Hospital
  Recruiting

• Oropharyngeal Immunoprophylaxis With High Polyphenolic Olive Oil as Clinical Spectrum Mitigating Factor in COVID-19. - Condition:   COVID-19
  Intervention:   Dietary Supplement: High polyphenolic olive oil. (Early harvest olive oil).
  Sponsor:   Hospital General Nuestra Señora del Prado
  Completed

• A Randomized, Phase I Study of DNA Vaccine OC-007 as a Booster Dose of COVID-19 Vaccine - Conditions:   COVID-19 Respiratory Infection;   COVID-19 Vaccine Adverse Reaction
  Interventions:   Biological: DNA vaccine OC-007;   Other: Placebo
  Sponsor:   Matti Sällberg
  Not yet recruiting

• Multicenter Randomized Double-blind Placebo-controlled Study to Investigate Azvudine in Symptomatic Adults With COVID-19 at Increased Risk of Progressing to Severe Illness - Condition:   COVID-19 Respiratory Infection
  Interventions:   Drug: Azvudine;   Drug: Placebo
  Sponsor:   Peking Union Medical College Hospital
  Not yet recruiting

• UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients With Refractory Hypoxia - Conditions:   Mesenchymal Stem Cell;   COVID-19 Pneumonia
  Intervention:   Biological: UC-MSCs treatment
  Sponsors:   Shanghai East Hospital;   Sir Run Run Shaw Hospital
  Recruiting

• Safety and Efficacy of the Therapy With BREINMAX® for the Treatment of Patients With Asthenia After COVID-19 - Conditions:   Asthenia;   COVID-19
  Interventions:   Drug: Ethyl methyl hydroxypyridine succinate + Meldonium;   Drug: Placebo
  Sponsor:   Promomed, LLC
  Completed

• Aerosolized Versus Intravenous Colistin-based Antimicrobial Regimens in Hospitalized COVID-19 Patients With Bacterial Coinfection: A Randomized Controlled Trial - Condition:   Secondary Bacterial Infection in COVID-19 Patients
  Intervention:   Drug: Colistin
  Sponsor:   Beni-Suef University
  Completed

From PubMed

• A Series of Adenosine Analogs as the First Efficacious Anti-SARS-CoV-2 Drugs against the B.1.1.529.4 Lineage: A Preclinical Repurposing Research Study - Given the rapid progression of the coronavirus disease 2019 (COVID-19) pandemic, an ultrafast response was urgently required to handle this major public crisis. To contain the pandemic, investments are required to develop diagnostic tests, prophylactic vaccines, and novel therapies. Lately, nucleoside analog (NA) antivirals topped the scene as top options for the treatment of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Meanwhile, the continuous…

• The impact of loneliness on compliance with COVID-19 prevention guidelines - Many individuals have been reluctant to follow the COVID-19 prevention guidelines (e.g., wearing a mask, physical distancing, and vigilant handwashing) set forth by the U.S. Center for Disease Control to reduce the spread of COVID-19. In this research, we use reciprocal altruism theory to investigate the role of loneliness and its impact on compliance with these guidelines. Our findings indicate that lonely individuals are less willing to comply with COVID-19 prevention guidelines than…

• B cell response after SARS-CoV-2 mRNA vaccination in people living with HIV - CONCLUSIONS: The mRNA vaccination against SARS-CoV-2 elicits humoral and B cell responses quantitatively similar between PLWHIV and HCs, but there are important differences in terms of antibody functionality and phenotypes of memory B cells, reinforcing the notion that tailored vaccination policies should be considered for these patients.

• Design, synthesis, docking, and biochemical characterization of non-nucleoside SARS-CoV-2 RdRp inhibitors - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic. The identification of effective antiviral drugs remains an urgent medical need. In this context, here we report 17 new 1,4-benzopyrone derivatives, which have been designed, synthesized, and characterized for their ability to block the RNA-dependent RNA polymerase (RdRp) enzyme, a promising target for antiviral drug discovery. This compound series represents a good starting point for developing…

• Broadly neutralizing aptamers to SARS-CoV-2: a diverse panel of modified DNA antiviral agents - Since its discovery COVID-19 has rapidly spread across the globe with a massive toll on human health with infection mortality rates as high as 10% and a crippling impact on the world economy. Despite numerous advances there remains an urgent need for accurate and rapid point-of-care diagnostic tests, and better therapeutic treatment options. To contribute chemically distinct, non-protein-based affinity reagents, we report here the identification of modified DNA-based aptamers that selectively…

• Functional nucleic acids as potent therapeutics against SARS-CoV-2 infection - The COVID-19 pandemic has posed a severe threat to human life and the global economy. Although conventional treatments, including vaccines, antibodies, and small-molecule inhibitors, have been broadly developed, they usually fall behind the constant mutation of SARS-CoV-2, due to the long screening process and high production cost. Functional nucleic acid (FNA)-based therapeutics are a newly emerging promising means against COVID-19, considering their timely adaption to different mutants and…

• Protein post-translational modification in SARS-CoV-2 and host interaction - SARS-CoV-2 can cause lung diseases, such as pneumonia and acute respiratory distress syndrome, and multi-system dysfunction. Post-translational modifications (PTMs) related to SARS-CoV-2 are conservative and pathogenic, and the common PTMs are glycosylation, phosphorylation, and acylation. The glycosylation of SARS-CoV-2 mainly occurs on spike (S) protein, which mediates the entry of the virus into cells through interaction with angiotensin-converting enzyme 2. SARS-CoV-2 utilizes glycans to…

• Inhibitory effect of phytochemicals towards SARS-CoV-2 papain like protease (PLpro) proteolytic and deubiquitinase activity - Recent studies have shown that RNA-dependent RNA polymerase (RdRp), 3-chymotrypsin-like protease (3CLpro), and papain-like protease (PLpro) are necessary for SARS-CoV-2 replication. Among these three enzymes, PLpro exhibits both proteolytic and deubiquitinase (DUB) activity and is responsible for disrupting the host’s innate immune response against SARS-CoV-2. Because of this unique property of PLpro, we investigated the inhibitory effects of phytochemicals on the SARS-CoV-2 PLpro enzyme. Our…

• Quercetin as a possible complementary agent for early-stage COVID-19: Concluding results of a randomized clinical trial - Background: Quercetin, a natural polyphenol with demonstrated broad-spectrum antiviral, anti-inflammatory, and antioxidant properties, has been proposed as an adjuvant for early-stage coronavirus disease 2019 (COVID-19) infection. Objective: To explore the possible therapeutic effect of quercetin in outpatients with early-stage mild to moderate symptoms of COVID-19. Methods: This was an open-label randomized controlled clinical trial conducted at the department of medicine, King Edward Medical…

• A Selective SARS-CoV-2 Host-Directed Antiviral Targeting Stress Response to Reactive Oxygen Species - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) catalyzed the development of vaccines and antivirals. Clinically approved drugs against SARS-CoV-2 target the virus directly, which makes them susceptible to viral mutations, which in turn can attenuate their antiviral activity. Here we report a host-directed antiviral (HDA), piperlongumine (PL), which exhibits robust antiviral activity as a result of selective induction of reactive oxygen species in infected cells by…

• Robust Covalent Aptamer Strategy Enables Sensitive Detection and Enhanced Inhibition of SARS-CoV-2 Proteins - Aptamer-based detection and therapy have made substantial progress with cost control and easy modification. However, the conformation lability of an aptamer typically causes the dissociation of aptamer-target complexes during harsh washes and other environmental stresses, resulting in only moderate detection sensitivity and a decreasing therapeutic effect. Herein, we report a robust covalent aptamer strategy to sensitively detect nucleocapsid protein and potently neutralize spike protein…

• Targeting an evolutionarily conserved “E-L-L” motif in spike protein to identify a small molecule fusion inhibitor against SARS-CoV-2 - As newer variants of SARS-CoV-2 continue to pose major threats to global human health and economy, identifying novel druggable antiviral targets is the key toward sustenance. Here, we identify an evolutionarily conserved “Ex(3)Lx(6)L” (“E-L-L”) motif present within the HR2 domain of all human and nonhuman coronavirus spike (S) proteins that play a crucial role in stabilizing its postfusion six-helix bundle (6-HB) structure and thus, fusion-mediated viral entry. Mutations within this motif reduce…

• Broad-spectrum antiviral inhibitors targeting pandemic potential RNA viruses - RNA viruses continue to remain a clear and present threat for potential pandemics due to their rapid evolution. To mitigate their impact, we urgently require antiviral agents that can inhibit multiple families of disease-causing viruses, such as arthropod-borne and respiratory pathogens. Potentiating host antiviral pathways can prevent or limit viral infections before escalating into a major outbreak. Therefore, it is critical to identify broad-spectrum antiviral agents. We have tested a small…

• A Systematic Survey of Reversibly Covalent Dipeptidyl Inhibitors of the SARS-CoV-2 Main Protease - SARS-CoV-2 is the coronavirus pathogen of the currently prevailing COVID-19 pandemic. It relies on its main protease (M ^(Pro) ) for replication and pathogenesis. M ^(Pro) is a demonstrated target for the development of antivirals for SARS-CoV-2. Past studies have systematically explored tripeptidyl inhibitors such as nirmatrelvir as M ^(Pro) inhibitors. However, dipeptidyl inhibitors especially those with a spiro residue at their P2 position have not been systematically investigated. In this…

• Extremely potent pan-sarbecovirus neutralizing antibodies generated by immunization of macaques with an AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2 - The rapid emergence of SARS-CoV-2 variants that evade immunity to vaccination has placed a global health imperative on the development of therapeutic countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent pan-sarbecovirus antibodies from non-human primates vaccinated with an AS03 adjuvanted subunit vaccine against SARS-CoV-2 that recognize conserved epitopes in the receptor binding domain (RBD) with femtomolar affinities….

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