Background: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a respiratory illness that has led to millions of deaths worldwide and has been declared a pandemic. Most antiviral treatments are targeted toward patients with severe or moderate-to-severe illness or those at high risk of developing severe COVID-19. Limited options exist for patients with mild-to-moderate COVID-19, irrespective of vaccination history or the risk of developing severe illness. Ensitrelvir is a novel oral SARS-CoV-2 3C-like protease inhibitor that has shown promising results in phase 2 studies in treating mild-to-moderate COVID-19. Here we describe the protocol for a phase 3 study designed to evaluate the efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19, regardless of risk status or history of vaccination. Methods: This is a multicenter, randomized, double-blind, placebo-controlled, phase 3 study. A total of 1590 patients with mild-to-moderate COVID-19 will be enrolled and randomized in 1:1:1 ratio into 3 treatment arms - ensitrelvir 125 mg (375 mg as loading dose on Day 1), ensitrelvir 250 mg (750 mg as loading dose on Day 1), or placebo. Patients will be administered the study interventions orally once daily for 5 days. Treatment outcomes will include efficacy and safety assessments. The primary endpoint will be the time to resolution of COVID-19 symptoms (including 12 symptoms listed in a partially modified index prescribed by the Food and Drug Administration). The three key secondary endpoints will be the change from baseline on Day 4 in the amount of SARS-CoV-2 viral RNA, the time to the first negative SARS-CoV-2 viral titer, and the proportion of participants without resolution of COVID-19 symptoms 3 weeks after administration. All safety assessments and adverse events will be reported. Discussion: Time to resolution of COVID-19 symptoms is a suitable endpoint to assess antiviral treatment in these patients. In phase 2a and 2b studies, ensitrelvir has been demonstrated to have antiviral efficacy against SARS-CoV-2 and a trend toward reducing time to resolution of symptoms in patients with mild-to-moderate COVID-19. Through this study, we seek to validate and further establish the clinical efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19. Trial registration: Japan Registry of Clinical Trials (https://jrct.niph.go.jp): jRCT2031210350.
In the absence of a systematic approach to epidemiological modeling in Slovenia, various isolated mathematical epidemiological models emerged shortly after the outbreak of the COVID-19 epidemic. We present an epidemiological model adapted to the COVID-19 situation in Slovenia. The standard SEIR model was extended to distinguish between age groups, symptomatic or asymptomatic disease progression, and vaccinated or unvaccinated populations. Evaluation of the model forecasts for 2021 showed the expected behavior of epidemiological modeling: our model adequately predicts the situation up to 4 weeks in advance; the changes in epidemiologic dynamics due to the emergence of a new viral variant in the population or the introduction of new interventions cannot be predicted by the model, but when the new situation is incorporated into the model, the forecasts are again reliable. Comparison with ensemble forecasts for 2022 within the European Covid-19 Forecast Hub showed better performance of our model, which can be explained by a model architecture better adapted to the situation in Slovenia, in particular a refined structure for vaccination, and better parameter tuning enabled by the more comprehensive data for Slovenia. Our model proved to be flexible, agile, and, despite the limitations of its compartmental structure, heterogeneous enough to provide reasonable and prompt short-term forecasts and possible scenarios for various public health strategies. The model has been fully operational on a daily basis since April 2020, served as one of the models for decision-making during the COVID-19 epidemic in Slovenia, and is part of the European Covid-19 Forecast Hub.
Background and Objectives: Eating disorders (EDs) are undertreated worldwide. In the UK the lag between recognition of symptoms and treatment ranges from about 15 months to in excess of two years. Internet-based Cognitive Behaviour Therapy (ICBT) could be a viable alternative to face-to-face Cognitive Behaviour Therapy (CBT) that avoids the negative impacts of delayed interventions. Based on evidence from randomised controlled trials (RCTs) this systematic review investigated the effectiveness of minimally guided self-help ICBT, without face-to-face therapy, for the prevention, treatment and relapse prevention of all types of EDs in adults. Methods: The electronic databases MEDLINE, PsychINFO, CENTRAL, Scopus, and Web of Science were searched between 1991 to 2021. Inclusion criteria specified RCTs with ICBT versus inactive comparison groups. The Cochrane Risk of Bias Tool was used for quality assessments. Qualitative synthesis and meta-analyses were conducted. Results: Findings showed medium and large significant beneficial effect sizes for the prevention and treatment studies, respectively, whereas relapse prevention yielded mainly small non-significant beneficial effect sizes. Only the treatment studies reached clinical significance and cognitive symptoms improved more than behavioural symptoms. Conclusions: This systematic review reinforces the vital need to provide evidence-based Internet interventions at times when face-to-face treatment is not an option as has been the case during the COVID-19 pandemic. Although ICBT is a promising intervention for eating disorders in adults and may be more effective than face-to-face CBT for treating cognitive symptoms further high-quality ED RCTs are required to increase the evidence-base and enable more precise meta-analyses to reach definitive conclusions.
Importance: Assessing relative disease severity of SARS-CoV-2 variants in populations with varied vaccination and infection histories can help characterize emerging variants and support healthcare system preparedness. Objective: To assess COVID-19 hospitalization risk for patients infected with Omicron (BA.1 and sublineages) compared with Delta SARS-CoV-2 variants. Design: Observational cohort study. Setting: New York City Department of Health and Mental Hygiene population-based COVID-19 disease registry, linked with laboratory results, immunization registry, and supplemental hospitalization data sources. Participants: New York City residents with positive laboratory-based SARS-CoV-2 tests during August 2021-January 2022. A secondary analysis restricted to patients with whole-genome sequencing results, comprising 1%-18% of weekly confirmed cases. Exposures: Diagnosis during periods when ≥98% of sequencing results were Delta (August-November 2021) or Omicron (January 2022). A secondary analysis defined variant exposure using patient-level sequencing results. Main outcomes and measures: COVID-19 hospitalization, defined as a positive SARS-CoV-2 test 14 days before or 3 days after hospital admission. Results: Among 646,852 persons with a positive laboratory-based SARS-CoV-2 test, hospitalization risk was lower for patients diagnosed when Omicron predominated (16,025/488,053, 3.3%) than when Delta predominated (8,268/158,799, 5.2%). In multivariable analysis adjusting for demographic characteristics and prior diagnosis and vaccination status, patients diagnosed when Omicron relative to Delta predominated had 0.72 (95% confidence interval [CI]: 0.63, 0.82) times the hospitalization risk. In a secondary analysis of 55,138 patients with sequencing results, hospitalization risk was similar for patients infected with Omicron (2,042/29,866, 6.8%) relative to Delta (1,780/25,272, 7.0%) and higher among those who received two mRNA vaccine doses (adjusted relative risk 1.64, 95% CI: 1.44, 1.87). Conclusions and relevance: Illness severity was lower for patients diagnosed when Omicron (BA.1 and sublineages) relative to Delta predominated. This finding was consistent after adjusting for prior diagnosis and vaccination status, suggesting intrinsic virologic properties, not population-based immunity, accounted for the lower severity. A secondary analysis demonstrated collider bias from the sequencing sampling frame changing over time in ways associated with disease severity. Investing in representative data collection is necessary to avoid bias in assessing relative disease severity as new variants emerge, immunity wanes, and additional COVID-19 vaccines are administered.
Influenza circulation declined during the COVID-19 pandemic. The timing and extent of decline and its association with interventions against COVID-19 were described for some regions. Here, we provide a global analysis of the influenza decline between March 2020 and September 2021 and investigate its potential drivers. We computed influenza change by country and trimester relative to the 2014-2019 period using the number of samples in the FluNet database. We used random forests to determine important predictors in a list of 20 covariates including demography, weather, pandemic preparedness, COVID-19 incidence, and COVID-19 pandemic response. With a regression tree we then classified observations according to these predictors. We found that influenza circulation decreased globally, with COVID-19 incidence and pandemic preparedness being the two most important predictors of this decrease. The regression tree showed interpretable groups of observations by country and trimester: Europe and North America clustered together in spring 2020, with limited influenza decline despite strong COVID-19 restrictions; in the period afterwards countries of temperate regions, with high pandemic preparedness, high COVID-19 incidence and stringent social restrictions grouped together having strong influenza decline. Conversely, countries in the tropics, with altogether low pandemic preparedness, low reported COVID-19 incidence and low strength of COVID-19 response showed low influenza decline overall. A final group singled out four “zero-Covid” countries, with the lowest residual influenza levels. The spatiotemporal decline of influenza during the COVID-19 pandemic was global, yet heterogeneous. The sociodemographic context and stage of the COVID-19 pandemic showed non-linear associations with this decline. Zero-Covid countries maintained the lowest levels of reduction with strict border controls and despite close-to-normal social activity. These results suggest that the resurgence of influenza could take equally diverse paths. It also emphasizes the importance of influenza reseeding in driving countries9 seasonal influenza epidemics.
Background and Aims: Vitamin D deficiency has been reported to associate with impaired development of antigen-specific responses following vaccination. We aimed to determine whether vitamin D supplements might boost immunogenicity and efficacy of SARS-CoV-2 vaccination. Methods: We conducted three sub-studies nested within the CORONAVIT randomised controlled trial, which investigated effects of offering vitamin D supplements at a dose of 800 or 3200 IU per day vs. no offer on risk of acute respiratory infections, including COVID-19, in UK adults with circulating 25-hydroxyvitamin D concentrations under 75 nmol/L. Sub-study 1 (n=2808) investigated effects of vitamin D supplementation on risk of breakthrough SARS-CoV-2 infection following two doses of SARS-CoV-2 vaccine. Sub-study 2 (n=1853) investigated effects of vitamin D supplementation on titres of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies in eluates of dried blood spots collected after SARS-CoV-2 vaccination. Sub-study 3 (n=100) investigated effects of vitamin D supplementation on neutralising antibody and cellular responses in venous blood samples collected after SARS-CoV-2 vaccination. Results: 1945/2823 (69.3%) sub-study 1 participants received two doses of ChAdOx1 nCoV-19 (Oxford AstraZeneca); the remainder received two doses of BNT162b2 (Pfizer). Vitamin D supplementation did not influence risk of breakthrough SARS-CoV-2 infection (800 IU per day vs. no offer: adjusted hazard ratio 1.28, 95% CI 0.89 to 1.84; 3200 IU per day vs. no offer: 1.17, 0.81 to 1.70). Neither did it influence IgGAM anti-Spike titres, neutralising antibody titres or interferon-gamma concentrations in supernatants of S peptide-stimulated whole blood. Conclusions: Among adults with sub-optimal baseline vitamin D status, vitamin D replacement at a dose of 800 or 3200 IU per day did not influence protective efficacy or immunogenicity of SARS-CoV-2 vaccination. Clinical Trial Registration: ClinicalTrials.gov NCT04579640.
Background: In early 2020, following the start of the coronavirus disease 2019 (COVID-19) pandemic, institutions of higher education (IHEs) across the United States rapidly pivoted to distance learning to reduce risk of on-campus virus transmission. Objective: To explore IHE use of nonpharmaceutical interventions (NPIs) during the subsequent pandemic-affected academic year 2020—2021. Design: Cross-sectional study of data collected January — June 2021. Setting: US four-year, undergraduate IHEs. Patients (or Participants): All public (n=547) and a stratified random sample of private (n=300) IHEs. Measurements: From IHE websites, we documented NPIs, including changes to the calendar, learning environment, housing, common areas, and dining; COVID-19 testing; and facemask protocols, and performed weighted analysis to assess congruence with the US Centers for Disease Control and Prevention (CDC) guidance for IHEs. We used weighted multivariable linear regression to explore the association between IHE characteristics and the summated number of implemented NPIs. Results: Overall, 20% of IHEs implemented all surveyed CDC-recommended NPIs. The most frequently utilized were learning environment changes (91%), practiced as one or more of the following: distance or hybrid learning opportunities (98%), 6-feet spacing (60%), and reduced class sizes (51%). Additionally, 88% of IHEs specified facemask protocols, 78% physically modified common areas, and 67% offered COVID-19 testing. Among the 33% of IHEs offering ≥50% of courses in person, having <1,000 students was associated with having implemented fewer NPIs than IHEs with ≥1,000 students. Limitations: Data collected from publicly available sources may introduce observation biases but allow for large sample size. Conclusion: Only 1 in 5 IHEs implemented all surveyed CDC recommendations, while a majority implemented a subset. IHE size and location were associated with degree of NPI implementation. Additional research is needed to assess adherence to NPI implementation in IHE settings.
People are more likely to interact with other people of their ethnicity - a phenomenon known as ethnic homophily. In the United States, people of color are known to hold proportionately more high-contact jobs and are thus more at risk of virus infection. At the same time, these ethnic groups are on average younger than the rest of the population. This gives rise to interesting disease dynamics and non-trivial trade-offs that should be taken into consideration when developing prioritization strategies for future mass vaccine roll-outs. Here, we study the spread of COVID-19 through the U.S. population, stratified by age, ethnicity, and occupation, using a detailed, previously-developed compartmental disease model. Based on historic data from the U.S. mass COVID-19 vaccine roll-out that began in December 2020, we show, (i) how ethnic homophily affects the choice of optimal vaccine allocation strategy, (ii) that, notwithstanding potential ethical concerns, differentiating by ethnicity in these strategies can improve outcomes (e.g., fewer deaths), and (iii) that the most likely social context in the United States is very different from the standard assumptions made by models which do not account for ethnicity and this difference affects which allocation strategy is optimal.
Background. It is widely reported that the SARS-CoV-2 Omicron variant has resulted in high number of cases, but relatively low incidence of severe disease and deaths, compared to the pre-Omicron variants of concern. We aim to assess the differences in symptom prevalence between Omicron and pre-Omicron infections in a sub-Saharan African population. Methods. In this cross-sectional observational study, we collected data from children and adult outpatients presenting at two primary healthcare facilities in Blantyre, Malawi. Eligible participants were aged >1month old, with signs suggestive of COVID-19, and those not suspected of COVID-19. Nasopharyngeal swabs were collected for SARS-CoV-2 PCR testing and positive samples whole genome sequenced to identify the infecting variant. The primary outcome was the likelihood of presenting with a given symptom in individuals testing positive during the period in which Omicron-dominated (December 2021 to March 2022) with those infected during the pre-Omicron period (August 2021 to November 2021). Findings. Among 5176 study participants, the median age was 28 years (IQR 21-38), of which 6.4% were under 5, 9.2% were 6 to 17 years, 77% were 18 to 50 years, and 7.1% were above 50 years old. Prevalence of SARS-CoV-2 infection was 23% (1187/5188), varying over time, with peaks in January 2021, July 2021 and December 2021, driven by the Beta (B.1.351), Delta (B.1.617.2) and Omicron (BA.1/2) variants, respectively. Headache (OR 0.47[CI 0.29 - 0.79]), cough (OR 0.37[CI 0.22 - 0.61]), fatigue (OR 0.20[CI 0.08 - 0.48]) and abdominal pain (OR 0.38[CI 0.18 - 0.78]) were less common in participants infected during the Omicron-dominant period than during pre-Omicron period. Fever was more common in participants infected during the Omicron-dominated period than during pre-Omicron period (OR 2.46[CI 1.29 - 4.97]). COVID-19 vaccination, accounting for number of doses and days since last dose, was not associated with a reduced risk of PCR-confirmed SARS-CoV-2 infection (1 dose, OR 1.10[CI 0.39 - 2.66]; 2 doses, OR 1.11[CI 0.40 - 2.57]; all p=0.8). Interpretation. In this Malawian population, the prevalence of clinical symptoms associated with Omicron infection differ from those of pre-Omicron infections and may be harder to identify clinically with current symptom guidelines. To maintain robust surveillance for COVID-19 and emerging variants, case definitions and testing policies will need to be regularly reviewed to ensure case ascertainment.
Abstract Since the outbreak of COVID-19 on 31 December 2019, different public health systems have been grappling with how to address the spread of the virus. During the cholera outbreak and the Covid-19 pandemic in Zambia, values such as equity, partnership and collaboration have been recognized as central to resilience and an effective response to the pandemic. In this study we identify lessons that can be used for addressing the COVID-19 pandemic from partnership approach used in confronting the cholera outbreak of 2017-2018 in Zambia Chipata Compound. Method: Data was collected using a qualitative approach; 26 interviews were conducted with Public Health Professionals and community Leaders. Document reviews from government institutions and non-government institutions were also conducted. The Bergen model of Collaborative Functioning was used to guide the analysis of data. Results: A top-down approach was observed to be important in addressing cholera but there was a need to improve a bottom-up approach. Synergistic results, avoidance of duplication, Oral cholera vaccination intervention and collaborative capacity building. Challenges in the partnership collaboration included inadequate resources, poor communication, poor coordination, lack of clear shared vision, reactive response, poor involvement of the community, hegemonic powers and mistrust and resentment Conclusion: From the experience of cholera outbreaks, partnerships are vital in addressing pandemics. Based on the lessons from the cholera outbreaks, we note that there is a need to improve collaboration in partnership if COVID-19 and cholera are to be effectively addressed.
Variants of concern (VOC) of SARS-CoV2 and waning immunity pose a serious global problem. Herein, we aimed to identify novel correlates of protection (COPs) against symptomatic SARS-CoV-2 infection. We conducted a Multicenter prospective study assessing the association between serological profiles and the risk for SARS-CoV-2 infection, comparing those vaccinated with three to four doses of Pfizer BNT162b2 vaccine. Of 608 healthy adults, 365 received three doses and 243 received four doses. During the first 90 days of followup, 239 (39%) were infected, of whom 165/365 (45%) received 3 doses and 74/243 (30%) four doses. We found that the fourth dose elicited a significant rise in antibody binding and neutralizing titers against multiple variants, and reduced the risk of symptomatic infection by 37% [95% I, 15% - 54%]. We found several binding IgG and IgA markers and their combinations that were COPs. The strongest association with infection risk was IgG levels to RBD mutants and IgA levels to VOCs, which was a COP in the three-dose group (HR=6.34, p=0.008) and in the four-dose group (HR=8.14, p=0.018). A combination of two commercially available ELISA assays were also associated with protection in both groups (HR = 1.84, p = 0.002; HR = 2.01, p = 0.025, respectively). In a subset, comparing those with low to high antibody levels before 4th dose, despite a significant rise in neutralizing antibody titers against both omicron variants, the number of infections in the low group (n=16) was significantly higher than in the high group (n=7, 43% vs. 20%, p=0.051). We demonstrated that following immunization with three or four vaccine doses, combinations of IgA and IgG levels are associated with protection from symptomatic infection. In addition, we identified a subpopulation of healthy adult individuals with low-baseline levels of antibodies after 3 doses which are at an increased risk for SARS-CoV-2 infection despite receiving a fourth dose. These findings warrant further study of this group, assessing whether they are at a higher risk for developing severe disease or may spread infection more readily than others.
Bank of Human Leukocytes From COVID-19 Convalescent Donors With an Anti-SARS-CoV-2 Cellular Immunity - Condition: COVID-19
Intervention: Other: Generation of a biobank allowing the cryopreservation of leucocytes from COVID19 convalescent donors
Sponsor: Central Hospital, Nancy, France
Not yet recruiting
Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients - Condition: Severe COVID-19
Interventions: Biological: Coronavirus-2-specific T cells; Other: standard of care (SOC)
Sponsors: George Papanicolaou Hospital; General Hospital Of Thessaloniki Ippokratio
Recruiting
A Randomised, Multi-centre, Double-blind, Phase 3 Study to Observe the Effectiveness, Safety and Tolerability of Molnupiravir Compared to Placebo Administered Orally to High-risk Adult Outpatients With Mild COVID-19 Receiving Local Standard of Care in South Africa - Condition: COVID-19
Intervention: Drug: Molnupiravir 200 mg
Sponsors: University of Witwatersrand, South Africa; Bill and Melinda Gates Foundation
Not yet recruiting
Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study) - Condition: COVID-19
Interventions: Drug: FB2001; Drug: FB2001 placebo
Sponsor: Frontier Biotechnologies Inc.
Not yet recruiting
Engaging Staff to Improve COVID-19 Vaccination Response at Long-Term Care Facilities - Condition: COVID-19
Interventions: Behavioral: Full Intervention; Other: Enhanced Usual Care
Sponsors: Kaiser Permanente; Patient-Centered Outcomes Research Institute; Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)
Recruiting
A Study to Evaluate the Efficacy of PanCytoVir™ for the Treatment of Non-Hospitalized Patients With COVID-19 Infection - Condition: COVID-19
Interventions: Drug: PanCytoVir™ (probenecid); Drug: Placebo
Sponsor: TrippBio, Inc.
Not yet recruiting
Value of Montelukast as a Potential Treatment of Post COVID-19 Persistent Cough - Condition: Post COVID-19
Intervention: Drug: Montelukast Sodium Tablets
Sponsor: Assiut University
Completed
Topical Antibacterial Agents for Prevention of COVID-19 - Conditions: COVID-19; SARS-CoV2 Infection
Interventions: Drug: Neosporin; Other: Vaseline
Sponsors: Yale University; Bill and Melinda Gates Foundation
Not yet recruiting
**NanoMn®_COVID-19 A Prospective, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blind Trial to Evaluate the Clinical Efficacy of NanoManganese® on Top of Standard of Care, in Adult Patients With Moderate to Severe Coronavirus Disease 2019 (COVID-19)** - Condition: COVID-19 Pandemic
Interventions: Drug: Placebo; Drug: Experimental drug
Sponsor: Medesis Pharma SA
Recruiting
Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study - Condition: Post-COVID19 Condition
Interventions: Combination Product: Plasma Exchange Procedure; Other: Sham Plasma Exchange Procedure
Sponsors: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; IrsiCaixa; Banc de Sang i Teixits
Not yet recruiting
Evaluation of Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection - Conditions: COVID-19; Rehabilitation
Interventions: Other: Respiratory training with the use of resistance set on respiratory muscle trainer; Other: Respiratory training without resistance set on respiratory muscle trainer
Sponsor: Medical University of Bialystok
Recruiting
Developing an Integrative, Recovery-Based, Post-Acute COVID-19 Syndrome (PACS) Psychotherapeutic Intervention - Condition: Post-acute COVID-19 Syndrome
Intervention: Behavioral: PACS Coping and Recovery (PACS-CR) Intervention
Sponsor: VA Office of Research and Development
Not yet recruiting
Mineralocorticoid Use in COVID-19 Patients - Conditions: COVID-19; ARDS
Intervention: Drug: Fludrocortisone Acetate 0.1 MG
Sponsor: Ain Shams University
Completed
A Dose Escalation Phase 1 Study Evaluating the Safety and Pharmacokinetics of an Inhaled COVID-19 Inhibitor Delcetravir in Healthy Subjects - Condition: COVID-19
Intervention: Combination Product: Delcetravir dry powder inhaler
Sponsor: Esfam Biotech Pty Ltd
Not yet recruiting
A Study to Evaluate the Safety and Immunogenicity of Ad5-vector Based Vaccine Against Coronavirus Variants in Adults (≥18 Years) Immunized With 2 Doses of mRNA Vaccines Plus One Dose of Booster AZD1222 Vaccine - Condition: COVID-19
Interventions: Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector); Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) for Inhalation; Biological: mRNA-based COVID-19 vaccine
Sponsor: CanSino Biologics Inc.
Not yet recruiting
Evaluation of apigenin-based biflavonoid derivatives as potential therapeutic agents against viral protease (3CLpro) of SARS-CoV-2 via molecular docking, molecular dynamics and quantum mechanics studies - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic COVID-19 disease that affects human respiratory function. Despite the scientific progression made in the development of the vaccine, there is an urgent need for the discovery of antiviral drugs for better performance at different stages of SARS-CoV-2 reproduction. The main protease (Mpro or 3CLpro) plays a pivotal role in the life cycle of the virus, making it an attractive target for the…
Variations of SARS-CoV-2 in the Iranian population and candidate putative drug-like compounds to inhibit the mutated proteins - The first cases of the novel coronavirus, SARS-CoV-2, were detected in December 2019 in Wuhan, China. Nucleotide substitutions and mutations in the SARS-CoV-2 sequence can result in the evolution of the virus and its rapid spread across the world. Therefore, understanding genetic variants of SARS-CoV-2 and targeting the conserved elements responsible for viral replication have great benefits for detecting its infection sources and diagnosing and treating COVID-19. In this study, we used the…
Synthesis, spectral characterization, crystal structure and computational investigation of 2-formyl-6-methoxy-3-carbethoxy quinoline as potential SARS-CoV inhibitor - The recent COVID-19 outbreak caused by the novel coronavirus SARS-CoV-2 has an immense impact on global health and economy. Although vaccines are being used, urgent need of drugs based on natural products with high efficacy and safety is a pressing priority. Quinoline alkaloids are well known for their therapeutic action against malaria; initially, it was tried against Coronaviruses. It is a basic vital scaffold to design drugs with required biological and pharmacological activities. In this…
The Anti-Histamine Azelastine, Identified by Computational Drug Repurposing, Inhibits Infection by Major Variants of SARS-CoV-2 in Cell Cultures and Reconstituted Human Nasal Tissue - Background and purpose: The COVID-19 pandemic continues to pose challenges, especially with the emergence of new SARS-CoV-2 variants that are associated with higher infectivity and/or compromised protection afforded by the current vaccines. There is a high demand for additional preventive and therapeutic strategies effective against this changing virus. Repurposing of approved or clinically tested drugs can provide an immediate solution. Experimental Approach: We applied a novel computational…
Discovery of TCMs and derivatives against the main protease of SARS-CoV-2 via high throughput screening, ADMET analysis, and inhibition assay in vitro - The rapidly evolving Coronavirus Disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide with thousands of deaths and infected cases. For the identification of effective treatments against this disease, the main protease (M^(pro)) of SARS‑CoV‑2 was found to be an attractive drug target, as it played a central role in viral replication and transcription. Here, we report the results of high-throughput molecular docking with…
Carlina oxide inhibits the interaction of SARS-CoV-2 S glycoprotein with angiotensin-converting enzyme 2 - Carlina acaulis plant is a potential target for the industrial production of phytochemicals that display applicability in pharmacy and medicine. The dry roots of C. acaulis contain up to 2 % of essential oil, the main component (up to 99 %) of which is carlina oxide [2-(3-phenylprop-1-ynyl)furan]. This compound shows multidirectional biological activity, including antibacterial and antifungal properties. Here, we evaluated the capacity of carlina oxide to inhibit the interaction between…
Protein-protein conjugation enhances immunogenicity of SARS-CoV-2 Receptor Binding Domain (RBD) vaccines - Several effective SARS-CoV-2 vaccines have been developed using different technologies. Although these vaccines target the isolates collected early in the pandemic, many have protected against serious illness from newer variants. Nevertheless, efficacy has diminished against successive variants and the need for effective and affordable vaccines persists especially in the developing world. Here, we adapted our protein-protein conjugate vaccine technology to generate a vaccine based on receptor…
Conserved 3’ UTR of Severe Acute Respiratory Syndrome Coronavirus 2: Potential Therapeutic Targets - Our previous paper showed that microRNAs (miRNAs) present within human placental or mesenchymal stem cell-derived extracellular vesicles (EVs) directly interacted with the RNA genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), inhibiting viral replication. In this paper, we analyzed whether these miRNAs could exert antiviral activity against other variants of SARS-CoV-2. We downloaded compete SARS-CoV-2 genome data submitted to the National Center for Biotechnology…
Paxlovid: Mechanism of Action, Synthesis, and In Silico Study - In this work, the discovery and description of PF-07321332, a major bioavailable oral SARS-CoV-2 protease inhibitor with in vitro human coronavirus antiviral activity, and excellent selection of off-target and in vivo immune profiles are reported. Various drugs and novel compound candidates for the treatment of the COVID-19 pandemic have been developed. PF-07321332 (or nirmatrelvir) is a new oral antiviral drug developed by Pfizer. In response to the pandemic, Pfizer has developed the COVID…
The SARS-CoV-2 main protease (Mpro): Structure, function, and emerging therapies for COVID-19 - The main proteases (M^(pro)), also termed 3-chymotrypsin-like proteases (3CL^(pro)), are a class of highly conserved cysteine hydrolases in β-coronaviruses. Increasing evidence has demonstrated that 3CL^(pro)s play an indispensable role in viral replication and have been recognized as key targets for preventing and treating coronavirus-caused infectious diseases, including COVID-19. This review is focused on the structural features and biological function of the severe acute respiratory syndrome…
Lopinavir-menthol co-crystals for enhanced dissolution rate and intestinal absorption - Lopinavir is an antiretroviral, antiparasitic agent and recently utilized in treatment of COVID-19. Unfortunately, lopinavir exhibited poor oral bioavailability due to poor dissolution, extensive pre-systemic metabolism, and significant P-glycoprotein intestinal efflux. Accordingly, the aim was to enhance dissolution rate and intestinal absorption of lopinavir. This employed co-processing with menthol which is believed to modify crystalline structures and inhibit intestinal efflux. Lopinavir was…
Cellular and Humoral Immune Response to a Third Dose of BNT162b2 COVID-19 Vaccine - A Prospective Observational Study - CONCLUSION: This study detected a BMI-dependent antibody increase after the third dose of BNT162b2 following different vaccination protocols. All participants showed a significant increase in their immune response. This, in combination with the low rate of post-vaccination-symptoms underlines the potential beneficial effect of a BNT162b2-booster dose.
Activation of the AIM2 Receptor in Circulating Cells of Post-COVID-19 Patients With Signs of Lung Fibrosis Is Associated With the Release of IL-1α, IFN-α and TGF-β - Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), responsible for COVID-19, has caused a global pandemic. Observational studies revealed a condition, herein called as Long-COVID syndrome (PC), that affects both moderately and severely infected patients, reducing quality-of-life. The mechanism/s underlying the onset of fibrotic-like changes in PC are still not well defined. The goal of this study was to understand the involvement of the Absent in melanoma-2 (AIM2) inflammasome in…
SARS-CoV-2 Achieves Immune Escape by Destroying Mitochondrial Quality: Comprehensive Analysis of the Cellular Landscapes of Lung and Blood Specimens From Patients With COVID-19 - Mitochondria get caught in the crossfire of coronavirus disease 2019 (COVID-19) and antiviral immunity. The mitochondria-mediated antiviral immunity represents the host’s first line of defense against viral infection, and the mitochondria are important targets of COVID-19. However, the specific manifestations of mitochondrial damage in patients with COVID-19 have not been systematically clarified. This study comprehensively analyzed one single-cell RNA-sequencing dataset of lung tissue and two…
1,2,3,4,6-Pentagalloyl glucose of Pistacia lentiscus can inhibit the replication and transcription processes and viral pathogenesis of SARS-COV-2 - SARS-COV-2 stands as the source of the most catastrophic pandemic of this century, known as COVID-19. In this regard, we explored the effects of five Pistaciasp. active ingredients on the most crucial targets of SARS-COV-2, including 3CLpro, PLpro, RdRp, helicase, NSP15, and E protein. The results of molecular docking determined 1,2,3,4,6-pentagalloyl glucose (PG) as the most effective compound of Pistaciasp, which also confirmed its excellent binding affinities and stable interactions with…