Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
1.
Viruses ; 12(7)2020 07 07.
Article in English | MEDLINE | ID: covidwho-639283

ABSTRACT

Standard precautions to minimize the risk of SARS-CoV-2 transmission implies that infected cell cultures and clinical specimens may undergo some sort of inactivation to reduce or abolish infectivity. We evaluated three heat inactivation protocols (56 °C-30 min, 60 °C-60 min and 92 °C-15 min) on SARS-CoV-2 using (i) infected cell culture supernatant, (ii) virus-spiked human sera (iii) and nasopharyngeal samples according to the recommendations of the European norm NF EN 14476-A2. Regardless of the protocol and the type of samples, a 4 Log10 TCID50 reduction was observed. However, samples containing viral loads > 6 Log10 TCID50 were still infectious after 56 °C-30 min and 60 °C-60 min, although infectivity was < 10 TCID50. The protocols 56 °C-30 min and 60 °C-60 min had little influence on the RNA copies detection, whereas 92 °C-15 min drastically reduced the limit of detection, which suggests that this protocol should be avoided for inactivation ahead of molecular diagnostics. Lastly, 56 °C-30 min treatment of serum specimens had a negligible influence on the results of IgG detection using a commercial ELISA test, whereas a drastic decrease in neutralizing titers was observed.


Subject(s)
Betacoronavirus , Containment of Biohazards/methods , Coronavirus Infections/virology , Pneumonia, Viral/virology , Serologic Tests/methods , Virus Inactivation , Antibodies, Neutralizing/immunology , Betacoronavirus/immunology , Containment of Biohazards/standards , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Enzyme-Linked Immunosorbent Assay , Hot Temperature , Humans , Neutralization Tests , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , Serologic Tests/standards
2.
Rev Med Virol ; 30(6): 1-10, 2020 11.
Article in English | MEDLINE | ID: covidwho-707429

ABSTRACT

The health emergency caused by the recent Covid-19 pandemic highlights the need to identify effective treatments against the virus causing this disease (SARS-CoV-2). The first clinical trials have been testing repurposed drugs that show promising anti-SARS-CoV-2 effects in cultured cells. Although more than 2400 clinical trials are already under way, the actual number of tested compounds is still limited to approximately 20, alone or in combination. In addition, knowledge on their mode of action (MoA) is currently insufficient. Their first results reveal some inconsistencies and contradictory results and suggest that cohort size and quality of the control arm are two key issues for obtaining rigorous and conclusive results. Moreover, the observed discrepancies might also result from differences in the clinical inclusion criteria, including the possibility of early treatment that may be essential for therapy efficacy in patients with Covid-19. Importantly, efforts should also be made to test new compounds with a documented MoA against SARS-CoV-2 in clinical trials. Successful treatment will probably be based on multitherapies with antiviral compounds that target different steps of the virus life cycle. Moreover, a multidisciplinary approach that combines artificial intelligence, compound docking, and robust in vitro and in vivo assays will accelerate the development of new antiviral molecules. Finally, large retrospective studies on hospitalized patients are needed to evaluate the different treatments with robust statistical tools and to identify the best treatment for each Covid-19 stage. This review describes different candidate antiviral strategies for Covid-19, by focusing on their mechanism of action.

3.
Sci Rep ; 10(1): 13093, 2020 08 04.
Article in English | MEDLINE | ID: covidwho-697117

ABSTRACT

A novel coronavirus, named SARS-CoV-2, emerged in 2019 in China and rapidly spread worldwide. As no approved therapeutics exists to treat COVID-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time-consuming stages of drug development. In this study, we screened the PRESTWICK CHEMICAL LIBRARY composed of 1,520 approved drugs in an infected cell-based assay. The robustness of the screen was assessed by the identification of drugs that already demonstrated in vitro antiviral effect against SARS-CoV-2. Thereby, 90 compounds were identified as positive hits from the screen and were grouped according to their chemical composition and their known therapeutic effect. Then EC50 and CC50 were determined for a subset of 15 compounds from a panel of 23 selected drugs covering the different groups. Eleven compounds such as macrolides antibiotics, proton pump inhibitors, antiarrhythmic agents or CNS drugs emerged showing antiviral potency with 2 < EC50 ≤ 20 µM. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study provides information for the selection of drugs to be further validated in vivo. Disclaimer: This study corresponds to the early stages of antiviral development and the results do not support by themselves the use of the selected drugs to treat SARS-CoV-2 infection.


Subject(s)
Betacoronavirus/physiology , Small Molecule Libraries/chemistry , Animals , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Betacoronavirus/isolation & purification , Caco-2 Cells , Cell Survival/drug effects , Chlorocebus aethiops , Coronavirus Infections/pathology , Coronavirus Infections/virology , Drug Approval , Drug Evaluation, Preclinical , Drug Repositioning , Humans , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Small Molecule Libraries/metabolism , Small Molecule Libraries/pharmacology , Vero Cells , Virus Replication/drug effects
4.
Nature ; 585(7826): 584-587, 2020 09.
Article in English | MEDLINE | ID: covidwho-664587

ABSTRACT

Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease1-3. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes COVID-19-worldwide but there is no definitive evidence that HCQ is effective for treating COVID-194-7. Here we evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (Vero E6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to a placebo treatment, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues. When the drug was used as a pre-exposure prophylaxis treatment, HCQ did not confer protection against infection with SARS-CoV-2. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral drug for the treatment of COVID-19 in humans.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Animals , Azithromycin/pharmacology , Azithromycin/therapeutic use , Chlorocebus aethiops , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Cytokines/blood , Disease Models, Animal , Female , Humans , Hydroxychloroquine/pharmacokinetics , Hydroxychloroquine/pharmacology , In Vitro Techniques , Kinetics , Macaca fascicularis , Male , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Pre-Exposure Prophylaxis , Respiratory Mucosa/cytology , Respiratory Mucosa/drug effects , Respiratory Mucosa/virology , Time Factors , Treatment Failure , Vero Cells , Viral Load/drug effects
5.
Emerg Infect Dis ; 26(9)2020 09.
Article in English | MEDLINE | ID: covidwho-614160

ABSTRACT

We spotted severe acute respiratory syndrome coronavirus 2 on polystyrene plastic, aluminum, and glass for 96 hours with and without bovine serum albumin (3 g/L). We observed a steady infectivity (<1 log10 drop) on plastic, a 3.5 log10 decrease on glass, and a 6 log10 drop on aluminum. The presence of proteins noticeably prolonged infectivity.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/transmission , Disease Transmission, Infectious , Fomites/virology , Pneumonia, Viral/transmission , Aluminum/analysis , Coronavirus Infections/virology , Glass/analysis , Humans , Pandemics , Plastics/analysis , Pneumonia, Viral/virology , Time Factors
6.
Viruses ; 12(6)2020 06 08.
Article in English | MEDLINE | ID: covidwho-574875

ABSTRACT

Clinical samples collected in coronavirus disease 19 (COVID-19), patients are commonly manipulated in biosafety level 2 laboratories for molecular diagnostic purposes. Here, we tested French norm NF-EN-14476+A2 derived from European standard EN-14885 to assess the risk of manipulating infectious viruses prior to RNA extraction. SARS-CoV-2 cell-culture supernatant and nasopharyngeal samples (virus-spiked samples and clinical samples collected in COVID-19 patients) were used to measure the reduction of infectivity after 10 minute contact with lysis buffer containing various detergents and chaotropic agents. A total of thirteen protocols were evaluated. Two commercially available formulations showed the ability to reduce infectivity by at least 6 log 10, whereas others proved less effective.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/virology , Pneumonia, Viral/virology , Virus Inactivation/drug effects , Animals , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , Cell Culture Techniques/methods , Chlorocebus aethiops , Containment of Biohazards/methods , Containment of Biohazards/standards , Humans , Nasopharynx/virology , Pandemics , RNA, Viral/isolation & purification , Specimen Handling/methods , Vero Cells , Viral Load/methods
8.
Antiviral Res ; 177: 104762, 2020 05.
Article in English | MEDLINE | ID: covidwho-4426

ABSTRACT

Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.


Subject(s)
Antiviral Agents/therapeutic use , Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Antiviral Agents/standards , Betacoronavirus/drug effects , China , Chloroquine/adverse effects , Chloroquine/pharmacology , Chloroquine/standards , Clinical Trials as Topic/standards , Humans , Hydroxychloroquine/adverse effects , Hydroxychloroquine/pharmacology , Hydroxychloroquine/standards , Hydroxychloroquine/therapeutic use , Pandemics
SELECTION OF CITATIONS
SEARCH DETAIL