Abstract
A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has been the cause of a recent global pandemic. The highly contagious nature of this life-threatening virus makes it imperative to find therapies to counteract its diffusion. The main protease (Mpro) of SARS-CoV-2 is a promising drug target due to its indispensable role in viral replication inside the host. Using a combined two-steps approach of virtual screening and molecular docking techniques, we have screened an in-house collection of small molecules, mainly composed of natural and nature-inspired compounds. The molecules were selected with high structural diversity to cover a wide range of chemical space into the enzyme pockets. Virtual screening experiments were performed using the blind docking mode of the AutoDock Vina software. Virtual screening allowed the selection of structurally heterogeneous compounds capable of interacting effectively with the enzymatic site of SARS-CoV-2 Mpro. The compounds showing the best interaction with the protein were re-scored by molecular docking as implemented in AutoDock, while the stability of the complexes was tested by molecular dynamics. The most promising candidates revealed a good ability to fit into the protein binding pocket and to reach the catalytic dyad. There is a high probability that at least one of the selected scaffolds could be promising for further research
Highlights
The new SARS-like severe pneumonia illness was first identified among the workers in the Huanan Fish and Seafood market in Wuhan, Hubei province, in December 2019 [1]
The compounds showing the best interaction with the protein were re-scored by molecular docking as implemented in AutoDock, while the stability of the complexes was tested by molecular dynamics
Using the criteria outlined above, virtual screening allowed us to select a small group of potentially active molecules on SARS-CoV-2 main protease (Mpro)
Summary
The new SARS-like severe pneumonia illness was first identified among the workers in the Huanan Fish and Seafood market in Wuhan, Hubei province, in December 2019 [1]. Sequencing of the complete genome on 13 January 2020 showed that it was a novel coronavirus (GenBank No. MN908947) [2], initially designated by the preliminary name 2019-nCoV and with the official name of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), while the disease caused by SARS-CoV-2 has been termed Coronavirus disease 2019 (COVID-19), and later evolved into a global pandemic [3]. The SARS-CoV-2 virus belongs to the family of Coronaviridae, and spreads widely among humans and other mammals, causing a wide range of infections from common cold symptoms to fatal diseases, such as severe respiratory syndrome [4]. SARS-CoV-2 is an enveloped positive-sense single-stranded RNA (ssRNA) virus, consisting of 29,903 nucleotides and two untranslated sequences of 254 nucleotides at the 50 and 229 nucleotides at the 30 ends, which compare it to SARS-CoV and Molecules 2020, 25, 3745; doi:10.3390/molecules25163745 www.mdpi.com/journal/molecules Molecules FOR PEER REVIEW.
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