Ethiopia is the second most populous country in Africa and the sixth most affected by COVID-19 on the continent. Despite having experienced five infection waves, >499 000 cases, and ~7 500 COVID-19-related deaths as of January 2023, there is still no detailed genomic epidemiological report on the introduction and spread of SARS-CoV-2 in Ethiopia. In this study, we reconstructed and elucidated the COVID-19 epidemic dynamics. Specifically, we investigated the introduction, local transmission, ongoing evolution, and spread of SARS-CoV-2 during the first four infection waves using 353 high-quality near-whole genomes sampled in Ethiopia. Our results show that whereas viral introductions seeded the first wave, subsequent waves were seeded by local transmission. The B.1.480 lineage emerged in the first wave and notably remained in circulation even after the emergence of the Alpha variant. The B.1.480 was out-competed by the Delta variant. Notably, Ethiopia lack of local sequencing capacity was further limited by sporadic, uneven, and insufficient sampling that limited the incorporation of genomic epidemiology in the epidemic public health response in Ethiopia. These results highlight Ethiopia role in SARS-CoV-2 dissemination and the urgent need for balanced, near-real-time genomic sequencing.
Background In England and Wales, cryptosporidiosis cases peak in spring and autumn, usually associated with zoonotic and environmental exposures (Cryptosporidium parvum, spring/autumn) and with overseas travel and water-based activities (Cryptosporidium hominis, autumn). Restrictions to control the COVID-19 pandemic prevented social mixing and access to swimming pools and restaurants for many months. Foreign travel from the UK also reduced by 74% in 2020. However, these restrictions potentially increased environmental exposures as people sought alternative countryside activities locally. To inform and strengthen surveillance programmes, we investigated the impact of COVID-19 restrictions on the epidemiology of C. hominis and C. parvum cases. MethodsCryptosporidium-positive stools, with case demographic data, are referred routinely for genotyping to the national Cryptosporidium Reference Unit (CRU). Cases were extracted from the CRU database (01 January 2015 to 31 December 2021). We defined two periods for pre- and post-COVID-19 restrictions implementation corresponding to the first UK-wide lockdown on 23 March 2020: pre-restrictions between week 1, 2015 and week 12, 2020, and post restrictions-implementation between week 13, 2020 and week 52, 2021. We conducted an interrupted time-series analysis, assessing differences in C. parvum and C. hominis incidence, trends and periodicity between these periods using negative binomial regression with linear-splines and interactions. Results There were 21,304 cases between 01 January 2015 and 31 December 2021 (C. parvum = 12,246; C. hominis = 9,058). Post restrictions-implementation incidence of C. hominis dropped by 97.5% (95%CI: 95.4%-98.6%; p<0.001). The decreasing incidence-trend observed pre-restrictions (IRR=0.9976; 95%CI: 0.9969-0.9982; p<0.001) was not observed post restrictions-implementation (IRR=1.0081; 95%CI: 0.9978-1.0186; p=0.128) due to lack of cases. No periodicity change was observed post restrictions-implementation. Where recorded, 22% of C. hominis cases had travelled abroad. There was also a strong social gradient, with those who lived in deprived areas experiencing a higher proportion of cases. This gradient did not exist post restrictions-implementation, but the effect was exacerbated for the most deprived: 27.2% of cases from the most deprived decile compared to 12.7% in the pre-restrictions period. For C. parvum, post restrictions-implementation incidence fell by 49.0% (95%CI: 38.4%-58.3%; p<0.001). There was no pre-restrictions incidence-trend (IRR=1.0003; 95%CI: 0.9997-1.0009; p=0.322) but a slight increasing incidence-trend existed post restrictions-implementation (IRR=1.0071; 95%CI: 1.0038-1.0104; p<0.001). A periodicity change was observed for C. parvum post restrictions-implementation, peaking one week earlier in spring and two weeks later in autumn. Where recorded, 8% of C. parvum cases had travelled abroad. The social gradient observed for C. parvum was inverse to that for C. hominis, and was stable pre-restrictions and post restrictions-implementation. ConclusionC. hominis cases were almost entirely arrested post restrictions-implementation, reinforcing that foreign travel is a major driver of seeding infections. Increased hand-hygiene, reduced social mixing, limited access to swimming pools and limited foreign travel affected incidence of most gastrointestinal (GI) pathogens, including Cryptosporidium, in the same period. C. parvum incidence fell sharply but recovered throughout the post restrictions-implementation period, back to pre-restrictions levels by the end of 2021; this is consistent with relaxation of restrictions, reduced compliance and increased countryside use. The effect on our results of changes in health-seeking behaviours, healthcare access and diagnostic laboratory practices post restrictions-implementation is uncertain, but it is likely that access to GPs and specimen referral rate to CRU decreased. Future exceedance reporting for C. hominis should exclude the post restrictions-implementation period but retain it for C. parvum (except the first six weeks post restrictions-implementation where the incidence fell sharply). Advice on infection prevention and control should be improved for people with GI symptoms, including returning travellers, to ensure hand hygiene and appropriate swimming pool avoidance.
Background Varied degrees of lockdown have been imposed for dozens of jurisdictions upon facing the SARS-CoV-2 epidemics during the past two years. Areal lockdown has been demonstrated effective to reduce the morbility and mortality of COVID-19. Even after the strict lockdown the peak of infection will appear around 9-25 days (median 18 days) thereafter. A wave of Omicron variant (BA.2 and BA.2.2) outbreak was seen from March to May 2022, in Shanghai, a megacity in China mainland. Aim To understand the sources of infection cases from outside or inside the isolated locations before and after the strict city lockdown. Methods The attributable addresses of SARS-CoV-2 infection were reported daily as well as the infected cases from March 18th, 2022 on through government website, which was publicly accessible. The address data and infected cases were collected until May 29th, 2022. The location (longitude and latitude) of these addresses were retrieved and the pattern of repeatedly reported addresses were analyzed. A tool of simple and meso-scale point-based (location-based) chronological graph was used to visualize and analyze the interactions of these locations. Results From March 18th to May 29th 2022, 173,350 items representing 35,743 unique addresses and 636,279 infected cases were released. The infection cases peaked 16 days after the city lockdown and were highly clustered in much crowded districts. The proportion of repeatedly reported locations of the previous day increased from around 20% before lockdown to greater than 40% in the plateau and remained at this level for up to one third (20/62) of the lockdown phase. This significantly increased proportion of intra-address infection indicated a pattern shift from inter-addresses to intra-address (D=0.2954, p<0.0001), which might perpetuate to the growth of infection cases. Based upon the day-to-day nearest neighbour transmission assumption the connections between some frequently repeated locations might be complex and heterogeneous. Interpretation During the strict areal isolation the intra-address infection may contribute significantly to infected cases of SARS-CoV-2 Omicron variant, the infection might have easily spilled over the boundary of family(with averaged family size of 2.3-3.1 people and family were required stay-at-home compulsively). This significant inter-addresses to intra-address pattern shift necessitated the understanding of intra-location transmission routes and corresponding interventions. Areal isolation and close off with homogeneous assumption inside and outside the isolated areas should be modified and the quantifing of the elevated risk for previously less exposed but much vulnerable sub-population was in pressing need.
Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine - either heterologous (PHH-1V group) or homologous (BNT162b2 group) - in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n=522) or BNT162b2 (n=260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p<0.0001), 1.31 (p=0.0007) and 0.86 (p=0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p<0.0001), 0.65 (p<0.0001) and 0.56 (p=0.003) for the Beta variant; 1.01 (p=0.92), 0.88 (p=0.11) and 0.52 (p=0.0003) for the Delta variant; and 0.59 (p=<0.0001), 0.66 (p<0.0001) and 0.57 (p=0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p=0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.
Introduction: We newly designed and developed two types of hydrogen fuel cell (HFC) buses (motorcoach type and minibus type) with a mobile laboratory system. Feasibility studies have been performed for mobile laboratory testing, especially for the laboratory performance of COVID-19 RT-PCR (PCR). Methods: We evaluated the driving range capability, PCR sample size capacity, turn-around time (TAT), and analytical performance for the detection of SARS-CoV-2. Saliva samples were used for the current research and the analytical performance was compared with reference PCR. Results: The estimated driving range and sample size capacity were 432 km and 3,258 samples, respectively for the HFC motorcoach and 313 km and 2,146 samples for the HFC minibus, respectively. For the TAT, the median time between the sample submission and the completion of PCR were 86 min for the motorcoach and 76 min for the minibus, and the median time between sample submission and the electronic reporting of the result to each visitor were 182 min for the motorcoach and 194 min for the minibus. A secondary analysis of 1,574 HFC mobile laboratory testing samples was conducted and all negative samples were negative by reference PCR. Furthermore, all positive samples were confirmed as positive by reference PCR or other molecular examinations. Conclusion: We confirmed the feasibility of HFC mobile laboratory systems for achieving the rapid reporting of highly accurate PCR results.
Background: Health services across the UK struggled to cope during the COVID-19 pandemic. Many treatments were postponed or cancelled, although the impact was mitigated by new models of delivery. While the scale of disruption has been studied, much less is known about if this disruption impacted health outcomes. The aim of our paper is to examine whether there is an association between individuals experiencing disrupted access to healthcare during the pandemic and risk of an avoidable hospitalisation. Methods: We used individual-level data for England from seven longitudinal cohort studies linked to electronic health records from NHS Digital (n = 29 276) within the UK Longitudinal Linkage Collaboration trusted research environment. Avoidable hospitalisations were defined as emergency hospital admissions for ambulatory care sensitive and emergency urgent care sensitive conditions (1st March 2020 to 25th August 2022). Self-reported measures of whether people had experienced disruption during the pandemic to appointments (e.g., visiting their GP or an outpatient department), procedures (e.g., surgery, cancer treatment) or medications were used as our exposures. Logistic regression models examined associations. Results: 35% of people experienced some form of disrupted access to healthcare. Those whose access was disrupted were at increased risk of any (Odds Ratio (OR) = 1.80, 95% Confidence Intervals (CIs) = 1.34-2.41), acute (OR = 1.68, CIs = 1.13-2.53) and chronic (OR = 1.93, CIs = 1.40-2.64) ambulatory care sensitive hospital admissions. There were positive associations between disrupted access to appointments and procedures to measures of avoidable hospitalisations as well. Conclusions: Our study presents novel evidence from linked individual-level data showing that people whose access to healthcare was disrupted were more likely to have an avoidable or potentially preventable hospitalisation. Our findings highlight the need to increase healthcare investment to tackle the short- and long-term implications of the pandemic beyond directly dealing with SARS-CoV-2 infections.
The emergence of Omicron subvariants and waning immunity to initial vaccine regimens led to the authorization of updated SARS-CoV-2 bivalent vaccines containing wildtype with either Omicron BA.1 or BA.4/5. Here, we compare early serologic responses from a randomized clinical trial of a second boost with either the Pfizer/BioNTech BNT162b2 (30 mcg dose) Wildtype/Omicron BA.1 or Wildtype/Omicron BA.4/5 vaccines against homologous and heterologous strains including contemporary Omicron subvariants BQ.1.1 and XBB.1.
Phase Ⅰ Clinical Trial of a Candidate COVID-19 Vaccine - Condition: COVID-19
Intervention: Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation
Sponsors: Wuhan BravoVax Co., Ltd.; National University Hospital, Singapore; Shanghai BravoBio Co., Ltd.
Not yet recruiting
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
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
INFLUENCE OF HIGH FREQUENCY CHEST WALL OSCILLATION IN HOSPITALIZED PATIENTS WITH COVID-19 - Condition: COVID-19
Intervention: Device: HIGH FREQUENCY CHEST WALL OSCILLATION
Sponsor: Cairo University
Not yet 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
The Difference Between Non-invasive High-frequency Oscillatory Ventilation and Non-invasive Continuous Airway Pressure Ventilation in COVID-19 With Acute Hypoxemia - Conditions: COVID-19 Pneumonia; Non-invasive Ventilation
Interventions: Device: Non-invasive high-frequency oscillatory ventilation; Device: Non-invasive continuous positive airway pressure ventilation
Sponsor: Guangzhou Institute of Respiratory Disease
Not yet recruiting
COVID-19 Molecular OTC At Home Test - Condition: COVID-19 Pandemic
Intervention: Diagnostic Test: Diagnostic Test: IN Vitro
Sponsor: 3EO Health
Not yet recruiting
Randomized-controlled Trial of Immunoadsorption (IA) in Patients With Chronic Fatigue Syndrome (CFS) Including Patients With Post-COVID-19 CFS (PACS-CFS) - Condition: ME/CSF Including CFS Related to Post-acute COVID-19 Syndrome (PACS)
Intervention: Device: Immunoadsorption
Sponsor: Charite University, Berlin, Germany
Not yet recruiting
Phase II/III Immunogenicity and Safety Study of the AVX/COVID-12 Vaccine Against COVID-19 Applied as a Booster. - Condition: SARS-CoV-2 Infection
Interventions: Biological: AVX-COVID/12; Biological: ChAdOx-1-S[recombinant]
Sponsors: Laboratorio Avi-Mex, S.A. de C.V.; National Council of Science and Technology, Mexico; Instituto Nacional de Enfermedades Respiratorias
Recruiting
Brain-Training Treatment for Long COVID in Older Adults - Condition: Post-Acute COVID-19 Syndrome
Intervention: Other: NeuroFlex (computerized gamified tasks)
Sponsor: UConn Health
Not yet recruiting
Phase 2/Phase 3 Study To Evaluate The Efficacy And Safety Of Ramatroban Along With The Standard Of Care In Subjects Hospitalized For COVID Pneumonia - Conditions: COVID-19 Pneumonia; COVID-19 Respiratory Infection
Interventions: Drug: Ramatroban; Drug: Placebo
Sponsors: KARE Biosciences; JSS Medical Research Inc.; Biomedical Advanced Research and Development Authority; Open Philanthropy; Charak Laboratories India Pvt. Ltd; Charak Foundation; BioLink Life Sciences, Inc.
Recruiting
The E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation - The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a severe global health crisis; its structural protein envelope (E) is critical for viral entry, budding, production, and induction of pathology which makes it a potential target for therapeutics against COVID-19. Here, we find that the E3 ligase RNF5 interacts with and catalyzes ubiquitination of E on the 63rd lysine, leading to its degradation by the…
SSRIs differentially modulate the effects of pro-inflammatory stimulation on hippocampal plasticity and memory via sigma 1 receptors and neurosteroids - Certain selective serotonin reuptake inhibitors (SSRIs) have anti-inflammatory effects in preclinical models, and recent clinical studies suggest that fluvoxamine can prevent deterioration in patients with COVID-19, possibly through activating sigma 1 receptors (S1Rs). Here we examined potential mechanisms contributing to these effects of fluvoxamine and other SSRIs using a well-characterized model of pro-inflammatory stress in rat hippocampal slices. When hippocampal slices are exposed acutely…
Inhibition of IL-6 signaling prevents serum-induced umbilical cord artery dysfunction from severe COVID-19 patients - Coronavirus disease 2019 (COVID-19) infection has a negative impact on the cytokine profile of pregnant women. Increased levels of pro-inflammatory cytokines seem to be correlated with the severity of the disease, in addition to predisposing to miscarriage or premature birth. Pro-inflammatory cytokines increase the generation of reactive oxygen species (ROS). It is unclear how interleukin-6 (IL-6) found in the circulation of severe COVID-19 patients might affect gestational health, particularly…
Emerging role of microRNAs and long non-coding RNAs in COVID-19 with implications to therapeutics - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which is commonly known as COVID-19 (COronaVIrus Disease 2019) has creeped into the human population taking tolls of life and causing tremendous economic crisis. It is indeed crucial to gain knowledge about their characteristics and interactions with human host cells. It has been shown that the majority of our genome consists of non-coding RNAs. Non-coding RNAs including micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs)…
Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection - Although the COVID-19 pandemic began over three years ago, the virus responsible for the disease, SARS-CoV-2, continues to infect people across the globe. As such, there remains a critical need for development of novel therapeutics against SARS-CoV-2. One technology that has remained relatively unexplored in COVID-19 is the use of antisense oligonucleotides (ASOs)-short single-stranded nucleic acids that bind to target RNA transcripts to modulate their expression. In this study, ASOs targeted…
Dantrolene and ryanodine receptors in COVID-19:The daunting taskand neglected warden - Dantrolene (DTN) is a ryanodine receptor (RyR) antagonist that inhibits Ca^(2+) release from stores in the sarcoplasmic reticulum. DTN is mainly used in the management of malignant hyperthermia. RyRs are highly expressed in immune cells and are involved in different viral infections, including SARS-CoV-2, since Ca^(2+) is necessary for viral replication, maturation, and release. DTN can inhibit the proliferation of SARS-CoV-2, indicating its potential role in reducing entry and pathogenesis of…
Modular Metal-Quinone Networks with Tunable Architecture and Functionality - Nanostructured materials with tunable structures and functionality are of interest in diverse areas. Herein, metal ions are coordinated with quinones via metal-acetylacetone coordination bonds to generate a class of structurally tunable, universally adhesive, superhydrophilic, and pH-degradable materials. A library of metal-quinone networks (MQNs) is produced from five model quinone ligands paired with nine metal ions, leading to particles, tubes, capsules, and films. Importantly, MQNs show…
Weathering and degradation of polylactic acid masks in a simulated environment in the context of the COVID-19 pandemic and their effects on the growth of winter grazing ryegrass - The COVID-19 pandemic has led to explosive growth in the production and consumption of disposable medical masks, which has caused new global environmental problems due to the improper disposal of these masks and lack of effective mask recycling methods. To reduce the environmental load caused by the inability of synthetic plastics to degrade, polylactic acid (PLA) masks, as a biodegradable environmentally friendly plastic, may become a solution. This study simulated the actual degradation…
Family functioning of families experiencing intensive care and the specific impact of the COVID-19 pandemic: A grounded theory study - CONCLUSION: There is awareness about the love that exists within the family. A willing to supporting each other in the family even if the critical illness made the family anxious and afraid.
Inhibiting the Deubiquitinase UCHL1 Reduces SARS-CoV-2 Viral Uptake by ACE2 - COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) remains a significant public health burden with limited treatment options. Many beta-coronaviruses, including SARS-CoV-2, gain entry to host cells through interaction of SARS-CoV-2 Spike (S) protein with membrane-bound angiotensin-converting enzyme 2 (ACE2). Given its necessity for SARS-CoV-2 infection, ACE2 represents a potential therapeutic target in COVID-19. However, early attempts…
Siglec-9 Restrains Antibody-Dependent Natural Killer Cell Cytotoxicity against SARS-CoV-2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters the immunological profiles of natural killer (NK) cells. However, whether NK antiviral functions are impaired during severe coronavirus disease 2019 (COVID-19) and what host factors modulate these functions remain unclear. We found that NK cells from hospitalized COVID-19 patients degranulate less against SARS-CoV-2 antigen-expressing cells (in direct cytolytic and antibody-dependent cell cytotoxicity [ADCC] assays)…
Discovery of Isojacareubin as a covalent inhibitor of SARS-CoV-2 main protease using structural and experimental approaches - The ongoing pandemic with the emergence of immune evasion potential and particularly the current omicron sub variants intensified the situation further. Although vaccine are available but the immune evasion capabilities of the recent variants demand further efficient therapeutic choices to control the SARS-CoV-2 pandemic. Hence, considering the necessity of the small molecule inhibitor we target the main protease (3CLpro) which is an appealing target for the development of anti-viral drugs…
A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo - The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron…
High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors - The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^(pro)) and papain like protease (PL^(pro)), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^(pro) inhibitors and 205 PL^(pro) inhibitors with low nmol/l activity of the best hits….
Kaempferol has potential anti-coronavirus disease 2019 (COVID-19) targets based on bioinformatics analyses and pharmacological effects on endotoxin-induced cytokine storm - COVID-19 has infected 272 million patients and caused 5.33 million deaths around the world, and it remains the main global threat. Previous studies revealed that Chinese traditional medicine is an effective treatment for COVID-19 infection. This study aims to reveal the pharmacological effects of kaempferol, which is the active component of Radix Bupleuri and Tripterygii Radix, and potential mechanisms for the treatment of COVID-19. Here, we employed the bioinformatics methods to filter the…