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1.
Am J Infect Control ; 50(3): 325-329, 2022 03.
Article in English | MEDLINE | ID: covidwho-1487575

ABSTRACT

BACKGROUND: The COVID-19 pandemic has had an unprecedented impact on global health and the world's economies. Proliferation of virulent and deadly SARS-CoV-2 variants require effective transmission mitigation strategies. Under reasonable environmental conditions, culturable and infectious SARS-CoV-2 can survive on contaminated fomites from hours to months. In the present study we evaluated a surface-anchored polymeric quaternary ammonium antimicrobial to help reduce fomite transmission of SARS-CoV-2 from contaminated surfaces. METHODS: Two studies were performed on antimicrobial pre-treated metal disks in March 2020 by two independent Biosafety Level III (BSL-3) equipped laboratories in April 2020. These facilities were in Belgium (the Rega Medical Research Institute) and Australia (the Peter Doherty Institute) and independently applied quantitative carrier-based methodologies using the authentic SARS-CoV-2 isolates (hCoV-19/Australia/VIC01/2020, hCoV-19/Belgium/GHB-03021/2020). RESULTS: Residual dry tests were independently conducted at both facilities and demonstrated sustained virion destruction (108.23 TCID50/carrier GHB-03021 isolate, and 103.66 TCID50/carrier VIC01 isolate) 1 hour (drying) + 10 minutes after inoculation. Reductions are further supported by degradation of RNA on antimicrobial-treated surfaces using qRT-PCR. CONCLUSIONS: Using a polymeric quaternary ammonium antimicrobial (EPA/PMRA registered) the results independently support a sustained antiviral effect via SARS-CoV-2 virion destruction and viral RNA degradation. This indicates that silane-anchored quaternary ammonium compound (SiQAC-18) treated surfaces could play an important role in mitigating the communicability and fomite transmission of SARS-CoV-2.


Subject(s)
Ammonium Compounds , COVID-19 , Fomites , Humans , Pandemics , SARS-CoV-2
2.
ACS Pharmacol Transl Sci ; 4(3): 1096-1110, 2021 Jun 11.
Article in English | MEDLINE | ID: covidwho-1313542

ABSTRACT

Compound repurposing is an important strategy for the identification of effective treatment options against SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (3CL-Pro), also termed M-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyproteins pp1a and pp1ab at multiple distinct cleavage sites. We here report the results of a repurposing program involving 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and small molecules regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro and have identified 62 additional compounds with IC50 values below 1 µM and profiled their selectivity toward chymotrypsin and 3CL-Pro from the Middle East respiratory syndrome virus. A subset of eight inhibitors showed anticytopathic effect in a Vero-E6 cell line, and the compounds thioguanosine and MG-132 were analyzed for their predicted binding characteristics to SARS-CoV-2 3CL-Pro. The X-ray crystal structure of the complex of myricetin and SARS-Cov-2 3CL-Pro was solved at a resolution of 1.77 Å, showing that myricetin is covalently bound to the catalytic Cys145 and therefore inhibiting its enzymatic activity.

3.
chemRxiv; 2021.
Preprint in English | ChemRxiv | ID: ppcovidwho-8730

ABSTRACT

A commercially available and EPA/PMRA registered quaternary ammonium antimicrobial formulation was applied to stainless steel carrier disks and sent to two virology research institutes to independently determine whether samples treated with SiQAC-C18 antimicrobial material could deactivate deposited SARS-CoV-2 virions on contaminated surfaces. The results independently support a sustained antiviral effect imparted from these treated surfaces by both SARS-CoV-2 virion destruction and degradation of viral RNA. These preliminary results indicate the SiQAC-18 treated surfaces could play an important role in mitigating the communicability and fomite transmission of SARS-CoV-2.

4.
Proc Natl Acad Sci U S A ; 117(43): 26955-26965, 2020 10 27.
Article in English | MEDLINE | ID: covidwho-841910

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effective treatment together with a lack of small animal infection models has led to clinical trials using repurposed drugs without preclinical evidence of their in vivo efficacy. We established an infection model in Syrian hamsters to evaluate the efficacy of small molecules on both infection and transmission. Treatment of SARS-CoV-2-infected hamsters with a low dose of favipiravir or hydroxychloroquine with(out) azithromycin resulted in, respectively, a mild or no reduction in virus levels. However, high doses of favipiravir significantly reduced infectious virus titers in the lungs and markedly improved lung histopathology. Moreover, a high dose of favipiravir decreased virus transmission by direct contact, whereas hydroxychloroquine failed as prophylaxis. Pharmacokinetic modeling of hydroxychloroquine suggested that the total lung exposure to the drug did not cause the failure. Our data on hydroxychloroquine (together with previous reports in macaques and ferrets) thus provide no scientific basis for the use of this drug in COVID-19 patients. In contrast, the results with favipiravir demonstrate that an antiviral drug at nontoxic doses exhibits a marked protective effect against SARS-CoV-2 in a small animal model. Clinical studies are required to assess whether a similar antiviral effect is achievable in humans without toxic effects.


Subject(s)
Amides/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Hydroxychloroquine/therapeutic use , Pyrazines/therapeutic use , Amides/pharmacokinetics , Animals , COVID-19/drug therapy , Chlorocebus aethiops , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Cricetinae , Disease Models, Animal , Disease Transmission, Infectious/prevention & control , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Female , Hydroxychloroquine/pharmacokinetics , Lung/drug effects , Lung/pathology , Lung/virology , Pyrazines/pharmacokinetics , SARS-CoV-2 , Treatment Outcome , Vero Cells , Viral Load/drug effects
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