Evaluation of 19 antiviral drugs against SARS-CoV-2 Infection

Abstract

The global pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) has prompted multiple clinical trials to jumpstart search for anti-SARS-CoV-2 therapies from existing drugs, including those with reported in vitro efficacies as well as those ones that are not known to inhibit SARS-CoV-2, such as ritonavir/lopinavir and favilavir. Here we report that after screening 19 antiviral drugs that are either in clinical trials or with proposed activity against SARS-CoV-2, remdesivir was the most effective. Chloroquine only effectively protected virus-induced cytopathic effect at around 30 µM with a therapeutic index of 1.5. Our findings also suggest that velpatasvir, ledipasvir, ritonavir, litonavir, lopinavir, favilavir, sofosbuvir, danoprevir, and pocapavir do not have direct antiviral effect.

Tenofovir and remdesivir ensemble docking with the SARS-CoV-2 polymerase and template-nascent RNA

“…Consistent with our findings, tenofovirdiphosphate has been shown to permanently terminate polymerase extension of nascent RNA when using recombinant RdRp-CoV2 [25]. However, infusion of tenofovir in Vero cell cultures did not inhibit replication of SARS-CoV-2 [26,27], while the use of 3-90 μM of its prodrug TDF yielded a 15-fold reduction of viral genome release [26] . Further, the use of TDF/FTC for treating SARS-CoV-2 infected ferrets led to better clinical scores and lower virus titers in nasal washes compared to a placebo [28].…”

Coronavirus RNA Proofreading: Molecular Basis and Therapeutic Targeting

“…A study using polymerase extension assays with a pre-annealed RNA template and primer and a pre-assembled SARS-CoV-2 nsp12-nsp8-nsp7 complex demonstrated that sofosbuvir could block chain extension ( Chien et al., 2020 ). However, a study that evaluated 19 potential anti-CoV drugs demonstrated that sofosbuvir failed to protect cells against SARS-CoV-2-induced cytopathic effects ( Liu et al., 2020 ). Further studies in vitro , in animal models, and in clinical trials are needed to establish whether this, or any drug under investigation, will be effective against CoVs.…”

Coronavirus disease 2019 (COVID-19): Immunological approaches and emerging pharmacologic treatments

“…Meanwhile, Zhu and colleagues [126] demonstrated that arbidol monotherapy was more effective than the use of lopinavir/ritonavir and arbidol. Besides, an in-vitro study performed on lopinavir did not exhibit any direct antiviral activity against SARS-CoV-2 [74] . Regardless of these findings, the administration of lopinavir/ritonavir seems beneficial on SARS-CoV and MERS-CoV only when used at the early stage of infection [127] .…”

“…Chloroquine and HCQ are both known as antimalarial drugs. Clinical studies introduced these two drugs as a possible choice for COVID-19 treatment due to having in-vitro antiviral and anti-inflammatory properties [71] , [72] , [73] , [74] . Several studies suggested that chloroquine could improve the radiological and virological features of COVID-19 [53] .…”