Drug repurposing and computational modeling for discovery of inhibitors of the main protease (M^pro) of SARS-CoV-2

Abstract

Structural and energetic features explain why some drugs can be repositioned to inhibit Mpro from SARS-CoV-2.

Identification of bioactive molecules from Triphala (Ayurvedic herbal formulation) as potential inhibitors of SARS-CoV-2 main protease (Mpro) through computational investigations

“…As a native ligand, the X77 forms H-bonds at residues Asn142 (2.16 Å), Gly143 (1.89 Å), His163 (1.67 Å), and Glu166 (2.05 Å), then H-carbon bonds at Thr26 (2.10 Å) and Met165 (2.90) and pi-pi stacked and pi-sulphur interactions at residues His41 (2.17 Å), Met49 (2.04 Å), and Cys145 (1.14 Å), respectively. These findings support previous findings that the selected compounds bind to the catalytic residues of M pro ( Silva et al, 2021 ). The substrate-binding cleft contains a catalytic dyad composed of His41 and Cys145, which is located between domain I and II at the N-terminus, and a hydrogen-bonded water molecule bound to His41 acts as a third component of the catalytic triad ( Tan et al, 2005 ).…”

COVID-19 and the Importance of Being Prepared: A Multidisciplinary Strategy for the Discovery of Antivirals to Combat Pandemics

“…For example, Ginsenoside has shown both antiviral [ 51 , 52 , 53 ] and anti-COVID-19 [ 54 ] activities. Josamycin is considered to have anti-COVID-19 activity [ 55 , 56 ] while Pepstatin A has been reported as antiviral [ 57 , 58 , 59 ] as well as a SARS-CoV-2 protease inhibitor [ 60 , 61 , 62 ]. As far as we know, no antiviral activity has been reported for Docetaxel, Molport-046-067-769, and Molport-046-568-802.…”

Alkaloids and Alkaloid-Like Compounds are Potential Scaffolds of Antiviral Agents against SARS-CoV-2 (COVID-19) Virus

“…The outbreak of SARS-CoV-2 virus in December 2019 has stimulated research on drug repurposing, which has initially been conducted by in silico molecular docking study. 6,7 Recently, many commonly used drugs have also been screened and tested for antiviral activity against SARS-CoV-2 virus. This section provides the information of antiviral alkaloids and alkaloid-like drugs or antiviral leads, which have potential use as antiviral drugs for the treatment of COVID-19.…”

“…Three core structures of heterocycles including phenothiazine (7), phenoxazine (8), and phenoxathiin (9) were tested against SARS-CoV virus (Figure 2), which was first found in Guandong, China, in 2002. 17 SARS-CoV virus causes influenza-like symptoms with high mortality rate.…”