The disinfection of air using Germicidal Ultraviolet light (GUV) is a long-standing technique, which has received intense attention during the COVID-19 pandemic. GUV generally uses UVC lamps as its light source, which are known to initiate photochemistry in air. However, the impact of GUV on indoor air quality and chemistry has not been investigated in detail, to our knowledge. In this study, we model the chemistry initiated by GUV at 254 or 222 nm (“GUV254” or “GUV222”) in a typical room with typical indoor pollutant levels, and for different ventilation levels. GUV254 is irritating for skin and eyes, has an occupational exposure limit, and thus these fixtures typically irradiate a smaller volume near the ceiling, or inside ventilation ducts. In contrast, GUV222 is described by some as harmless to skin or eyes due to rapid absorption in a very thin external layer. Our analysis showed that GUV254 is able to significantly photolyze O3, generating OH radicals, which initiates the oxidation of all indoor volatile organic compounds (VOCs). While secondary organic aerosol (SOA) can be formed as a product of VOC oxidation, most of SOA in our case studies is produced through GUV-independent terpene ozonolysis. GUV254-induced SOA formation is of the order of 0.1-1 μg m-3. GUV222 with the same effective virus removal rate makes a smaller impact on indoor air quality at mid to high ventilation rates, mainly because of the significantly lower UV irradiance needed and substantially less efficient O3 photolysis (for primary OH generation) than at 254 nm, while it has a higher impact than GUV254 when ventilation is poor due to a small but significant photochemical production of O3 at 222 nm.
Background: Measurement of SARS-CoV-2 antibody seropositivity is important to accurately understand exposure to infection and/or vaccination in specific populations. Methods: Children with or without prior SARS-CoV-2 infections, was enrolled in Calgary, Canada in 2020. Venous blood was sampled 4 times from July 2020 to April 2022 for SARS-CoV-2 nucleocapsid and spike antibodies. Demographic and clinical information was obtained including SARS-CoV-2 testing results and vaccination records. Results: 1035 children were enrolled and 88.9% completed all 4 visits; median age 9 years (IQR: 5,13); 519 (50.1%) female; and 815 (78.7%) Caucasian. Before enrollment, 118 (11.4%) had confirmed or probable SARS-CoV-2. By April 2022, 39.5% of previously uninfected participants had a SARS-CoV-2 infection. Nucleocapsid antibody seropositivity declined to 16.4% after more than 200 days after diagnosis. Spike antibodies remained elevated in 93.6% of unvaccinated children after more than 200 days after diagnosis. By April 2022, 408 (95.6%) children 12 years and older had received 2 or more vaccine doses, and 241 (61.6%) 5 to 11 year-old children had received 2 vaccine doses. At that time, all 685 vaccinated children had spike antibodies, compared with 94/176 (53.4%) of unvaccinated children. Conclusions: In our population, after the first peak of Omicron variant infections and introduction of COVID-19 vaccines for children, all vaccinated children had SARS-CoV-2 spike antibodies, in contrast to 53.4% of unvaccinated children. It is not yet known whether a high level of seropositivity at a point in time indicates sustained population-level protection against SARS-CoV-2 transmission or severe COVID-19 outcomes in children.
Background: Monitoring safety outcomes following COVID-19 vaccination is critical for understanding vaccine safety especially when used in key populations such as elderly persons age 65 years and older who can benefit greatly from vaccination. We present new findings from a nationally representative early warning system that may expand the safety knowledge base to further public trust and inform decision making on vaccine safety by government agencies, healthcare providers, interested stakeholders, and the public. Methods: We evaluated 14 outcomes of interest following COVID-19 vaccination using the US Centers for Medicare & Medicaid Services (CMS) data covering 30,712,101 elderly persons. The CMS data from December 11, 2020 through Jan 15, 2022 included 17,411,342 COVID-19 vaccinees who received a total of 34,639,937 doses. We conducted weekly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination. Findings: Four outcomes met the threshold for a statistical signal following Pfizer-BioNTech vaccination including pulmonary embolism (PE; RR=1.54), acute myocardial infarction (AMI; RR=1.42), disseminated intravascular coagulation (DIC; RR=1.91), and immune thrombocytopenia (ITP; RR=1.44). After further evaluation, only the RR for PE still met the statistical threshold for a signal; however, the RRs for AMI, DIC, and ITP no longer did. No statistical signals were identified following vaccination with either the Moderna or Janssen vaccines. Interpretation: This early warning system is the first to identify temporal associations for PE, AMI, DIC, and ITP following Pfizer-BioNTech vaccination in the elderly. Because an early warning system does not prove that the vaccines cause these outcomes, more robust epidemiologic studies with adjustment for confounding factors, including age and nursing home residency, are underway to further evaluate these signals. FDA strongly believes the potential benefits of COVID-19 vaccination outweigh the potential risks of COVID-19 infection.
Mycobacterium-w (Mw), was shown to boost adaptive natural killer (ANK) cells and protect against COVID-19 during the first wave of the pandemic. As a follow-up of the trial, 50 healthcare workers (HCW) who had received Mw in September 2020 and subsequently received at least one dose of ChAdOx1 nCoV-19 vaccine (Mw+ChAdOx1 group) were monitored for symptomatic COVID-19, during a major outbreak with the delta variant of SARS-CoV-2 (April-June, 2021), along with 201 HCW receiving both doses of the vaccine without Mw (ChAdOx1 group). Despite 48% having received just a single dose of the vaccine in Mw+ChAdOx1 group, only 2 had mild COVID-19, compared to 36 infections in the ChAdOx1 group (HR-0.46, p=0.009). Transcriptomic studies revealed an enhanced adaptive NK cell-dependent ADCC in the Mw+ChAdOx1 group, along with downregulation of TLR2-MYD88 pathway and concomitant attenuation of downstream inflammatory pathways. This might have resulted in robust protection during the pandemic with the delta variant.
Background: Our objective was to evaluate the real world effectiveness of nirmatrelvir/ritonavir to prevent severe COVID-19 while Omicron and its subvariants predominate. Methods: We conducted a population based cohort study in Ontario, Canada including all residents >17 years of age who tested positive for SARS-CoV-2 by PCR between 4 April and 31 August 2022. We compared nirmatrelvir/ritonavir treated patients to unexposed patients and measured the primary outcome of hospitalization or death from COVID-19, and a secondary outcome of death 1-30 days. We used weighted logistic regression to calculate weighted odds ratios (wOR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding. Results: The final cohort included 177,545 patients with 8,876 (5.0%) exposed and 168,669 (95.0%) unexposed individuals. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. Hospitalization or death within 30 days was lower in the nirmatrelvir/ritonavir treated group compared to unexposed individuals (2.1% vs 3.7%, wOR 0.56; 95%CI, 0.47-0.67). In the secondary analysis, the relative odds of death was also significantly reduced (1.6% vs 3.3%, wOR 0.49; 95%CI, 0.39-0.62). The number needed to treat to prevent one case of severe COVID-19 was 62 (95%CI 43 to 80). Findings were similar across strata of age, DDIs, vaccination status, and comorbidities. Interpretation: Nirmatrelvir/ritonavir was associated with significantly reduced risk of hospitalization and death from COVID-19 in this observational study, supporting ongoing use of this therapeutic to treat patients with mild COVID-19 at risk for severe disease.
Background: Post-acute sequelae of SARS-Co-V-2 infection (PASC) is associated with worsening diabetes trajectory. It is unknown whether PASC in children with type 1 diabetes (T1D) manifests as worsening diabetes trajectory. Objective: To explore the association between SARS-CoV-2 infection (COVID-19) and T1D-related healthcare utilization (for diabetic ketoacidosis [DKA] or severe hypoglycemia [SH]) or Hemoglobin (Hb) A1c trajectory. Methods: We included children <21 years with T1D and ≥1 HbA1c prior to cohort entry, which was defined as COVID-19 (positive diagnostic test or diagnosis code for COVID-19, multisystem inflammatory syndrome in children, or PASC) or a randomly selected negative test for those who were negative throughout the study period (Broad Cohort). A subset with ≥1 HbA1c value from 28-275 days after cohort entry (Narrow Cohort) was included in the trajectory analysis. Propensity score-based matched cohort design followed by weighted Cox regression was used to evaluate the association of COVID-19 with healthcare utilization >28 days after cohort entry. Generalized estimating equation models were used to measure change in HbA1c in the Narrow cohort. Results: From 03/01/2020-06/22/2022, 2,404 and 1,221 youth met entry criteria for the Broad and Narrow cohorts, respectively. The hazard ratio for utilization was (HR 1.45 [95%CI,0.97,2.16]). In the Narrow Cohort, the rate of change (slope) of HbA1c increased 91-180 days after cohort entry for those with COVID-19 (0.138 vs. -0.002, p=0.172). Beyond 180 days, greater declines in HbA1c were observed in the positive cohort (-0.104 vs. 0.008 per month, p=0.024). Conclusion: While a trend towards worse outcomes following COVID-19 in T1D patients was observed, these findings were not statistically significant. Continued clinical monitoring of youth with T1D following COVID-19 is warranted.
Background & Aims: Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019, commonly involving the gastrointestinal tract. Some children with MIS-C undergo appendectomy before the final diagnosis. There are several hypotheses explaining pathomechanism of MIS-C, with the central role of the viral antigen persistence in the gut, associated with lymphocyte exhaustion and immune system dysregulation. We aimed to examine appendectomy specimens obtained from MIS-C patients and analyze the pathological features of the disease and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in the appendix. Methods: In this cross-sectional study we included 21 children with MIS-C who underwent appendectomy before the final diagnosis. MIS-C patients were recruited from the Polish national registry of inflammatory syndromes in children. The control group included 21 sex- and age-matched children with acute appendicitis (AA) unrelated to SARS-CoV-2 infection. Histological evaluation involved hematoxylin and eosin staining and immunohistochemical identification of lymphocyte subpopulations, programmed cell death protein 1, and SARS-CoV-2 nucleocapsid antigen. Results: Appendices of MIS-C patients lacked neutrophilic infiltrate of muscularis propria typical for AA (14 vs 95%, p<0.001). The proportion of CD20+ to CD5+ cells was higher in patients with MIS-C (p 0.04), as well as the proportion of CD4+ to CD8+ (p <0.001). We found no proof of SARS-CoV-2 antigen presence, nor lymphocyte exhaustion, in the appendices of MIS-C patients. Conclusions: Our findings describe pathomorphological features of the appendix in MIS-C and argue against the central role of SARS-CoV-2 persistence in the gut and concomitant lymphocyte exhaustion as the major triggers of MIS-C.
Long Covid – the disease encompassing the post-acute sequelae of SARS-CoV-2 (PASC) – affects millions of people around the world. Prevention of PASC is an urgent public health priority. In this work, we aimed to examine whether treatment with nirmatrelvir in the acute phase of COVID-19 is associated with reduced risk of post-acute sequelae. We used the healthcare databases of the US Department of Veterans Affairs to identify users of the health system who had a SARS-CoV-2 positive test between March 01, 2022 and June 30, 2022, were not hospitalized on the day of the positive test, had at least 1 risk factor for progression to severe COVID-19 illness and survived the first 30 days after SARS-CoV-2 diagnosis. We identify those who were treated with oral nirmatrelvir within 5 days after the positive test (n=9217) and those who received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection (control group, n= 47,123). Inverse probability weighted survival models were used to estimate the effect of nirmatrelvir (versus control) on a prespecified panel of 12 post-acute COVID-19 outcomes and reported as hazard ratio (HR) and absolute risk reduction (ARR) in percentage at 90 days. Compared to the control group, treatment with nirmatrelvir was associated with reduced risk of PASC (HR 0.74 95% CI (0.69, 0.81), ARR 2.32 (1.73, 2.91)) including reduced risk of 10 of 12 post-acute sequelae in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (deep vein thrombosis, and pulmonary embolism), fatigue, liver disease, acute kidney disease, muscle pain, neurocognitive impairment, and shortness of breath. Nirmatrelvir was also associated with reduced risk of post-acute death (HR 0.52 (0.35, 0.77), ARR 0.28 (0.14, 0.41)), and post-acute hospitalization (HR 0.70 (0.61, 0.80), ARR 1.09 (0.72, 1.46)). Nirmatrelvir was associated with reduced risk of PASC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection. In sum, our results show that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe COVID-19 illness, treatment with nirmatrelvir within 5 days of a positive SARS-CoV-2 test was associated with reduced risk of PASC regardless of vaccination status and history of prior infection. The totality of findings suggests that treatment with nirmatrelvir during the acute phase of COVID-19 reduces the risk of post-acute adverse health outcomes.
Background: Limited data exist regarding longer-term antibody responses following three-dose COVID-19 vaccination, and the impact of a first SARS-CoV-2 infection during this time, in people living with HIV (PLWH) receiving suppressive antiretroviral therapy (ART). We quantified wild-type-(WT), Omicron BA.1- and Omicron BA.5-specific responses up to six months post-third dose in 64 PLWH and 117 controls who remained COVID-19-naive or experienced their first SARS-CoV-2 infection during this time. Design: Longitudinal observational cohort. Methods: We quantified WT- and Omicron-specific Anti-Spike receptor-binding domain IgG concentrations, ACE2 displacement activities and live virus neutralization at one, three and six months post-third vaccine dose. Results: Third doses boosted all antibody measures above two-dose levels, but BA.1-specific responses remained significantly lower than WT-specific ones, with BA.5-specific responses lower still. Serum IgG concentrations declined at similar rates in COVID-19-naive PLWH and controls post-third dose (median WT- and BA.1-specific half-lives were between 66-74 days for both groups). Antibody function also declined significantly yet comparably between groups: six months post-third dose, BA.1-specific neutralization was undetectable in >80% of COVID-19 naive PLWH and >90% of controls. Breakthrough SARS-CoV-2 infection boosted antibody concentrations and function significantly above vaccine-induced levels in both PLWH and controls, though BA.5-specific neutralization remained significantly poorer than BA.1 even post-breakthrough. Conclusions: Following three-dose COVID-19 vaccination, antibody response durability in PLWH receiving ART is comparable to controls. PLWH also mounted strong responses to breakthrough infection. Due to temporal response declines however, COVID-19-naive individuals, regardless of HIV status, would benefit from a fourth dose within 6 months of their third.
The research around the public9s usage of masks to prevent the spread of COVID-19 is developing quickly. In this work, we analyzed data from 50 nations to assess the long-term effectiveness of mask policies with different levels using the Poisson regression model and generalized linear mixed model. Over the long term, stricter obligatory mask regulations were linked to more stable patterns and slower increases in Covid-19 case occurrences. The mitigation of disease transmission by mask policies was shown to have substantial major impacts throughout the entire year of 2020, whereas the incidence of illness displays increasing trends over time under various policies. When compared to no mask policy deployment, mask policies might reduce incidence growth by 13.5% to 17.8%, although the incidence under every policy climbed 1.5% to 1.9% on average every ten days. The mask policy is effective in controlling illness, according to the bulk of the data shown above. This result confirms the mask policy9s importance as a governing approach in the context of the worldwide pandemic.
Using a Community-level Just-in-Time Adaptive Intervention to Address COVID-19 Testing Disparities - Condition: COVID-19
Interventions: Behavioral: Multi-Level Multi-Component Intervention (MLI); Behavioral: Community Just-In-Time Adaptive Intervention (Community JITAI)
Sponsors: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)
Active, not recruiting
Safety and Efficacy of Medications COVID-19 - Condition: Severe Covid-19
Intervention: Drug: Oral bedtime melatonin
Sponsor: Hospital San Carlos, Madrid
Completed
Use of Multiple Doses of Convalescent Plasma in Mechanically Intubated Patients With COVID-19 - Condition: COVID-19
Intervention: Biological: Multiple doses of anti-SARS-CoV-2 Convalescent Plasma
Sponsors: Hospital Regional Dr. Rafael Estévez; Complejo Hospitalario Dr. Arnulfo Arias Madrid; Hospital Santo Tomas; Hospital Punta Pacífica, Pacífica Salud; Insituto Conmemorativo Gorgas de Estudios para la Salud; Sociedad Panameña de Hematología; Institute of Scientific Research and High Technology Services (INDICASAT AIP); University of Panama; Sistema Nacional de Investigación de Panamá
Completed
Examining How a Facilitated Self-Sampling Intervention and Testing Navigation Intervention Influences COVID-19 Testing - Condition: COVID-19
Interventions: Behavioral: Facilitated Self-Sampling Intervention (FSSI); Behavioral: Testing Navigation Intervention (TNI).; Behavioral: Control
Sponsors: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)
Not yet recruiting
A Phase III of COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older - Condition: COVID-19
Interventions: Biological: EuCorVac-19; Biological: ChAdOx1
Sponsor: EuBiologics Co.,Ltd
Recruiting
Open Multicenter Study for Assessment of Efficacy and Safety of Molnupiravir in Adult Patients With COVID-19 - Condition: COVID-19
Interventions: Drug: Molnupiravir (Esperavir); Drug: Standard of care
Sponsor: Promomed, LLC
Completed
Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population - Condition: COVID-19
Interventions: Drug: nirmatrelvir/ritonavir; Drug: Standard of care
Sponsors: Promomed, LLC; Sponsor GmbH
Completed
Study Evaluating GS-5245 in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness - Condition: COVID-19
Interventions: Drug: GS-5245; Drug: GS-5245 Placebo
Sponsor: Gilead Sciences
Recruiting
Effects of Respiratory Muscle Training in Individuals With Long-term Post-COVID-19 Symptoms - Conditions: Covid19; Post-acute COVID-19 Syndrome
Interventions: Other: Inspiratory + expiratory muscle training group; Other: Inspiratory + expiratory muscle training sham group; Other: Exercise training program
Sponsors: Universidad Complutense de Madrid; Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid
Recruiting
Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) Phase III Clinical Trial - Conditions: COVID-19; Coronavirus Infections
Interventions: Biological: LIBP-Rec-Vaccine; Biological: BIBP-Rec-Vaccine; Biological: placebo
Sponsors: National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products Co Ltd.
Not yet recruiting
A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza - Conditions: Influenza, Human; COVID-19
Interventions: Biological: bivalent BNT162b2 (original/Omi BA.4/BA.5); Biological: qIRV (22/23); Biological: QIV
Sponsors: BioNTech SE; Pfizer
Not yet recruiting
Study to Evaluate Safety, Tolerability, Efficacy and Pharmacokinetics of ASC10 in Mild to Moderate COVID-19 Patients - Condition: SARS CoV 2 Infection
Interventions: Drug: ASC10; Drug: Placebo
Sponsor: Ascletis Pharmaceuticals Co., Ltd.
Not yet recruiting
A Phase I/II Study of GLB-COV2-043 as a COVID-19 Vaccine Booster - Condition: COVID-19
Interventions: Drug: GLB-COV2-043; Drug: BNT162b2/COMIRNATY®
Sponsor: GreenLight Biosciences, Inc.
Not yet recruiting
Safety and Efficacy of Intranasal Administration of Avacc 10 Vaccine Against COVID-19 in Healthy Volunteers - Condition: COVID-19
Interventions: Biological: Avacc 10; Combination Product: Outer Membrane Vesicles (OMV) : OMV alone in vehicle; Other: Placebo
Sponsors: Intravacc B.V.; Novotech (Australia) Pty Limited
Not yet recruiting
The Phase Ⅱ/Ⅲ Trial of LYB001 - Condition: COVID-19
Interventions: Biological: LYB001; Biological: Placebo
Sponsor: Yantai Patronus Biotech Co., Ltd.
Not yet recruiting
New thiophene-derived α-aminophosphonic acids: Synthesis under microwave irradiations, antioxidant and antifungal activities, DFT investigations and SARS-CoV-2 main protease inhibition - Four new α-aminophosphonic acids containing thiophene ring have been synthesized using simple, neat and catalyst-free conditions, more convenient and eco-friendly method under microwave irradiations. The structures of the title molecules have been confirmed by UV-Vis, FT-IR, ¹H NMR, ^(13)C NMR and ^(31)P NMR. Moreover, their antioxidant activity was evaluated using DPPH, ABTS and phenantroline methods; the obtained results indicate that the title molecules exhibit excellent activity better than…
Antifungal activity of Taurolidine against Mucorales: An in vitro study on clinical isolates - CONCLUSION: In conclusion, this is an updated experience of using taurolidine against Mucorales. However, our in-vitro findings need to be confirmed in well-designed clinical trials aimed at treating invasive Mucormycosis infections.
Dual-targeting cyclic peptides of receptor-binding domain (RBD) and main protease (Mpro) as potential drug leads for the treatment of SARS-CoV-2 infection - The receptor-binding domain (RBD) and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) play a crucial role in the entry and replication of viral particles, and co-targeting both of them could be an attractive approach for the treatment of SARS-CoV-2 infection by setting up a “double lock” in the viral lifecycle. However, few dual RBD/Mpro-targeting agents have been reported. Here, four novel RBD/Mpro dual-targeting peptides, termed as MRs 1-4, were…
Polyphenolic promiscuity, inflammation-coupled selectivity: Whether PAINs filters mask an antiviral asset - The Covid-19 pandemic has elicited much laboratory and clinical research attention on vaccines, mAbs, and certain small-molecule antivirals against SARS-CoV-2 infection. By contrast, there has been comparatively little attention on plant-derived compounds, especially those that are understood to be safely ingested at common doses and are frequently consumed in the diet in herbs, spices, fruits and vegetables. Examining plant secondary metabolites, we review recent elucidations into the…
Benchmarked molecular docking integrated molecular dynamics stability analysis for prediction of SARS-CoV-2 papain-like protease inhibition by olive secoiridoids - CONCLUSION: AutoDock Vina retrieved the active molecules accurately and predicted Demethyloleuropein aglycone as the best inhibitor of PLpro. The Arabian diet consisting of olive products rich in secoiridoids benefits from the PLpro inhibition property and reduces the risk of viral infection.
Antimicrobial activity effects of electrolytically generated hypochlorous acid-treated pathogenic microorganisms by isothermal kinetic simulation - This study involves isothermal kinetic simulation to evaluate the parameters of inhibition conditions for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) of high-risk pathogens. This is because the new type of the 2019 novel coronavirus (2019-nCoV) is continuously spreading and the importance of public health issues. Environmental disinfection and personal wearing of masks have become important epidemic prevention measures. Selection of concentration kinetics could be estimated…
Vimentin is an important ACE2 co-receptor for SARS-CoV-2 in epithelial cells - Vimentin is a type III intermediate filament protein, widely expressed in mesenchymal cells. Mainly located in the cytoplasm, vimentin can also appear at extracellular locations, where it may interact with bacterial or viral pathogens. In this study, we aimed at investigating the implication of vimentin in SARS-CoV-2 viral entry and the consequences on viral replication and cellular response. We showed that upon infection, vimentin was upregulated at the cell surface, where it interacts with…
Structure and inhibition of SARS-CoV-1 and SARS-CoV-2 main proteases by oral antiviral compound AG7404 - Severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2) pose a threat to global public health. The 3C-like main protease (M^(pro)), which presents structural similarity with the active site domain of enterovirus 3C protease, is one of the best-characterized drug targets of these viruses. Here we studied the antiviral activity of the orally bioavailable enterovirus protease inhibitor AG7404 against SARS-CoV-1 and SARS-CoV-2 from a structural, biochemical, and cellular…
A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors - Decoration of cap on viral RNA plays essential roles in SARS-CoV-2 proliferation. Here, we report a mechanism for SARS-CoV-2 RNA capping and document structural details at atomic resolution. The NiRAN domain in polymerase catalyzes the covalent link of RNA 5’ end to the first residue of nsp9 (termed as RNAylation), thus being an intermediate to form cap core (GpppA) with GTP catalyzed again by NiRAN. We also reveal that triphosphorylated nucleotide analog inhibitors can be bonded to nsp9 and fit…
Reduced circulating FABP2 in patients with moderate to severe COVID-19 may indicate enterocyte functional change rather than cell death - The gut is of importance in the pathology of COVID-19 both as a route of infection, and gut dysfunction influencing the severity of disease. Systemic changes caused by SARS-CoV-2 gut infection include alterations in circulating levels of metabolites, nutrients and microbial products which alter immune and inflammatory responses. Circulating plasma markers for gut inflammation and damage such as zonulin, lipopolysaccharide and β-glycan increase in plasma along with severity of disease. However,…
Generation of APN-chimeric gene-edited pigs by CRISPR/Cas9-mediated knock-in strategy - The prevalence of porcine enteric coronaviruses (PECs), including transmissible gastroenteritis virus (TGEV), swine acute diarrhea syndrome coronavirus (SADS-CoV), porcine delta coronavirus (PDCoV), and porcine epidemic diarrhea virus (PEDV), poses a serious threat to animal and public health. Here, we aimed to further optimize the porcine aminopeptidase N (pAPN) gene editing strategy to explore the balance between individual antiviral properties and the biological functions of pAPN in pigs….
SCUBE1 is associated with thrombotic complications, disease severity, and in-hospital mortality in COVID-19 patients - CONCLUSIONS: SCUBE1 may be one of the major determinants of thrombotic complications, which is an increased cause of mortality and morbidity in COVID-19 patients so inhibition of this peptide may be among the therapeutic targets in patients with COVID-19.
SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia - CONCLUSIONS: Coronaviruses, including SARS-CoV-2, cause AEC apoptosis, mitochondrial fission, and bioenergetic impairment. SARS-CoV-2 also suppresses HPV by targeting mitochondria. This mitochondriopathy is replicated by transduction with SARS-CoV-2 proteins, indicating a mechanistic role for viral-host mitochondrial protein interactions. Mitochondriopathy is a conserved feature of coronaviral pneumonia that may exacerbate hypoxemia and constitutes a therapeutic target.
An improved Fuzzy based GWO algorithm for predicting the potential host receptor of COVID-19 infection - Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has infected millions worldwide. SARS-CoV-2 spike protein uses Angiotensin-converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) for entering and fusing the host cell membrane. However, interaction with spike protein receptors and protease processing are not the only factors determining coronaviruses’ entry. Several proteases mediate the entry of SARS-CoV-2 virus into…
Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin - The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves dysregulations of iron metabolism, and although the mechanism of this pathology is not yet fully understood, correction of iron metabolism pathways seems a promising pharmacological target. The previously observed effect of inhibiting SARS-CoV-2 infection by ferristatin II, an inducer of transferrin receptor 1 (TfR1) degradation, prompted the study of competition between Spike protein and TfR1…