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1.
Viruses ; 12(6)2020 06 13.
Article in English | MEDLINE | ID: covidwho-602214

ABSTRACT

As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6.7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent sera and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here, we developed a neutralization assay using SARS-CoV-2 strain and Vero-E6 cells. We identified the most potent sera from recovered patients for the treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that a combination of orally available virus-directed nelfinavir and host-directed amodiaquine exhibited the highest synergy. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Neutralization Tests/methods , Pneumonia, Viral/drug therapy , Amodiaquine/pharmacology , Animals , Caco-2 Cells , Cell Line, Tumor , Chlorocebus aethiops , Coronavirus Infections/therapy , Drug Therapy, Combination , Emetine/pharmacology , HEK293 Cells , HT29 Cells , Homoharringtonine/pharmacology , Humans , Immune Sera/immunology , Immunization, Passive/methods , Nelfinavir/pharmacology , Pandemics , Pyrans/pharmacology , Pyrroles/pharmacology , Vero Cells
2.
Virol J ; 17(1): 71, 2020 06 03.
Article in English | MEDLINE | ID: covidwho-505653

ABSTRACT

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) of the family Coronaviridae has caused substantial economic losses in the swine husbandry industry. There's currently no specific drug available for treatment of coronaviruses or PEDV. METHOD: In the current study, we use coronavirus PEDV as a model to study antiviral agents. Briefly, a fusion inhibitor tHR2, recombinant lentivirus-delivered shRNAs targeted to conserved M and N sequences, homoharringtonine (HHT), and hydroxychloroquine (HCQ) were surveyed for their antiviral effects. RESULTS: Treatment with HCQ at 50 µM and HHT at 150 nM reduced virus titer in TCID50 by 30 and 3.5 fold respectively, and the combination reduced virus titer in TCID50 by 200 fold. CONCLUSION: Our report demonstrates that the combination of HHT and HCQ exhibited higher antiviral activity than either HHT or HCQ exhibited. The information may contribute to the development of antiviral strategies effective in controlling PEDV infection.


Subject(s)
Antiviral Agents/pharmacology , Homoharringtonine/pharmacology , Hydroxychloroquine/pharmacology , Porcine epidemic diarrhea virus/drug effects , RNA, Small Interfering/pharmacology , Animals , Chlorocebus aethiops , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Drug Synergism , Nucleocapsid Proteins/genetics , Peptides/pharmacology , RNA, Small Interfering/genetics , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/chemistry , Vero Cells , Viral Load/drug effects , Viral Matrix Proteins/genetics
3.
Antiviral Res ; 178: 104786, 2020 06.
Article in English | MEDLINE | ID: covidwho-30820

ABSTRACT

An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 µM, 26.63 µM, 2.55 µM and 0.46 µM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 µM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 µM in combination with emetine at 0.195 µM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.


Subject(s)
Antimetabolites/pharmacology , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Emetine/pharmacology , Homoharringtonine/pharmacology , Lopinavir/pharmacology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Virus Replication/drug effects , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Amides/pharmacology , Animals , Betacoronavirus/physiology , Chlorocebus aethiops , Drug Combinations , Epithelial Cells , Humans , Pandemics , Pyrazines/pharmacology , Ribavirin/pharmacology , Vero Cells
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