Abstract
AimsCoronavirus disease 2019 (COVID-19) has appeared in Wuhan, China but the fast transmission has led to its widespread prevalence in various countries, which has made it a global concern. Another concern is the lack of definitive treatment for this disease. The researchers tried different treatment options which are not specific. The current study aims to identify potential small molecule inhibitors against the main protease protein of SARS-CoV-2 by the computational approach. Main methodsIn this study, a virtual screening procedure employing docking of the two different datasets from the ZINC database, including 1615 FDA approved drugs and 4266 world approved drugs were used to identify new potential small molecule inhibitors for the newly released crystal structure of main protease protein of SARS-CoV-2. In the following to validate the docking result, molecular dynamics simulations were applied on selected ligands to identify the behavior and stability of them in the binding pocket of the main protease in 150 nanoseconds (ns). Furthermore, binding energy using the MMPBSA approach was also calculated. Key findingsThe result indicates that simeprevir (Hepatitis C virus NS3/4A protease inhibitor) and pyronaridine (antimalarial agent) could fit well to the binding pocket of the main protease and because of some other beneficial features including broad-spectrum antiviral properties and ADME profile, they might be a promising drug candidate for repurposing to the treatment of COVID-19. SignificanceSimeprevir and pyronaridine were selected by the combination of virtual screening and molecular dynamics simulation approaches as a potential candidate for treatment of COVID-19.
Highlights
Novel coronavirus, designated as COVID-19, was first identified in December 2019 in Wuhan, China [1]
COVID-19 is belongs to the Coronaviridae (CoV) family, enveloped positive-sense, singlestranded RNA viruses (+ssRNA) that are spread broadly among humans and other mammals that cause a wide range of infections from common cold symptoms to fatal disease like respiratory syndrome
The CoV genome is constantly changing due to the mutation processes such as insertion or deletion and recombination, COVID-19 is considered distinct from two high pathogenic SARS-CoV and MERS-CoV which are responsible for Severe Acute Respiratory Syndrome in 2002 and Middle East Respiratory Syndrome in 2012 respectively [2]
Summary
Novel coronavirus, designated as COVID-19, was first identified in December 2019 in Wuhan, China [1]. COVID-19 is belongs to the Coronaviridae (CoV) family, enveloped positive-sense, singlestranded RNA viruses (+ssRNA) that are spread broadly among humans and other mammals that cause a wide range of infections from common cold symptoms to fatal disease like respiratory syndrome. The CoV genome is constantly changing due to the mutation processes such as insertion or deletion and recombination, COVID-19 is considered distinct from two high pathogenic SARS-CoV and MERS-CoV which are responsible for Severe Acute Respiratory Syndrome in 2002 and Middle East Respiratory Syndrome in 2012 respectively [2]. The fatality rate of this new CoV, seems to be around 2 percent in China [3], which is much less than fatality rate of SARS and MERS. It should be consider that most of the fatal cases are vulnerable populations with medical condition such as immunosuppression, diabetes or heart disease. The point that has made it the global concern is the efficient transmission from human-to-human leading to its widespread outbreaks in many countries around the world [4]
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