Quantitative structure‐activity relationship and molecular docking revealed a potency of anti‐hepatitis C virus drugs against human corona viruses

Abstract

A number of human coronaviruses (HCoVs) were reported in the last and present centuries. Some outbreaks of which (eg, SARS and MERS CoVs) caused the mortality of hundreds of people worldwide. The problem of finding a potent drug against HCoV strains lies in the inability of finding a drug that stops the viral replication through inhibiting its important proteins. In spite of its limited efficacy and potential side effects, Ribavirin is extensively used as a first choice against HCoVs. Therefore, scientists reverted towards the investigation of different drugs that can more specifically target proteins. In this study, four anti-HCV drugs (one approved by FDA and others under clinical trials) are tested against HCoV polymerases. Quantitative Structure-Activity Relationship (QSAR) and molecular docking are both used to compare the performance of the selected nucleotide inhibitors to their parent nucleotides and Ribavirin. Both QSAR and molecular docking showed that IDX-184 is superior compared to Ribavirin against MERS CoV, a result that was also reported for HCV. MK-0608 showed a performance that is comparable to Ribavirin. We strongly suggest an in vitro study on the potency of these two drugs against MERS CoV.

COVID-19 spike-host cell receptor GRP78 binding site prediction

“…SARS and MERS HCoV are 10% and 36%, respectively. 8,[10][11][12][13] . COVID-19 has a 2% mortality rate, but only in a few months will we know how fast the new virus spreads.…”

“…HCoVs are positive-sense, long (30,000 bp) single-stranded RNA viruses. Two groups of proteins characterize HCoVs; structural proteins such as Spike (S) that characterize all coronaviruses, Nucleocapsid (N), Matrix (M), and Envelope (E), in addition to the non-structural proteins, such as proteases (nsp3 and nsp5) and RdRp (nsp12) 8,14 . The Spike protein is a crucial recognition factor for virus attachment and entry to the host cells.…”

“…COVID-19 is a member of Betacoronaviruses, like the former human coronaviruses SARS and MERS 8,9 . With this novel human coronavirus, there are now seven different strains of Human coronaviruses (HCoVs), namely, 229E and NL63 strains of HCoVs (Alphacoronaviruses), OC43, HKU1, SARS, MERS, and COVID-19 HCoVs (Betacoronaviruses) 1,8,10 . SARS and MERS HCoV are the widely known strains of coronaviruses, and each has caused about 800 deaths.…”

Anti-HCV, nucleotide inhibitors, repurposing against COVID-19

“…COVID-19 is a member of Betacoronaviruses like the Severe Acute Respiratory Syndrome Human coronavirus (SARS HCoV) and the Middle-East Respiratory Syndrome Human coronavirus (MERS HCoV) [10,11]. Until today, six different strains of Human coronaviruses (HCoVs) have been reported, in addition to the newly emerged COVID-19 [2,12].…”

“…Until today, six different strains of Human coronaviruses (HCoVs) have been reported, in addition to the newly emerged COVID-19 [2,12]. 229E and NL63 strains of HCoVs belong to Alphacoronaviruses while OC43, HKU1, SARS, MERS, and COVID-19 HCoVs belong to Betacoronaviruses [2,11]. SARS and MERS HCoV are the most aggressive strains of coronaviruses, leaving about 800 deaths each.…”