Identification of potential inhibitors of SARS-CoV-2 main protease and spike receptor from 10 important spices through structure-based virtual screening and molecular dynamic study

Abstract

The outbreak of novel coronavirus disease (COVID-19) caused by SARS-CoV-2 poses a serious threat to human health and world economic activity. There is no specific drug for the treatment of COVID-19 patients at this moment. Traditionally, people have been using spices like ginger, fenugreek and onion, etc. for the remedy of a common cold. This work identifies the potential inhibitors of the main protease (M pro) and spike (S) receptor of SARS-CoV-2 from 10 readily available spices. These two proteins, S and M pro , play an important role during the virus entry into the host cell, and replication and transcription processes of the virus, respectively. To identify potential molecules an in-house databank containing 1040 compounds was built-up from the selected spices. Structure-based virtual screening of this databank was performed with two important SARS-CoV-2 proteins using Glide. Top hits resulted from virtual screening (VS) were subjected to molecular docking using AutoDock 4.2 and AutoDock Vina to eliminate false positives. The top six hits against M pro and top five hits against spike receptor subjected to 130 ns molecular dynamic simulation using GROMACS. Finally, the compound 1-, 2-, 3and 5-M pro complexes, and compound 17-, 18-, 19-, 20and 21spike receptor complexes showed stability throughout the simulation time. The ADME values also supported the drug-like nature of the selected hits. These nine compounds are available in onion, garlic, ginger, peppermint, chili and fenugreek. All the spices are edible and might be used as home remedies against COVID-19 after proper biological evaluation.

Importance of glutamine 189 flexibility in SARS-CoV-2 main protease: Lesson learned from in silico virtual screening of ChEMBL database and molecular dynamics

“…Structure-based virtual screening of FDA-approved drug bank database that resulted in 20 hits against 3CLpro was performed by Chatterjee, Shilpa, et al ( Chatterjee et al, 2020 ) Recently, Sen et al virtually screened 10 important spices to identify potential inhibitors for both main protease and spike with the support of molecular dynamic simulations. ( Sen et al, 2020 ). Finally, Huynh et al, explored mechanisms of clinically oriented SARS-CoV-2 inhibitors including naturally occurring rutin as main protease inhbitors.…”

Insight into molecular characteristics of SARS-CoV-2 spike protein following D614G point mutation, a molecular dynamics study

“…According to available evidence, a spike mutant called spike D614G is more prevalent in some areas, especially in European countries, and has a higher mortality rate (Becerra-Flores & Cardozo, 2020 ; Eaaswarkhanth et al, 2020 ; Koyama et al, 2020 ). Although it was suggested that replacement of Asp614 (native form) with Gly reduces the affinity of the spike to bind to the hACE2 through surface, infectivity of the spike D614G is higher than native one (Sen, 2020 ). The present study aims to investigate the structural and molecular properties of mutant D614G by employing bioinformatics and molecular dynamics (MD).…”

Evaluation of traditional ayurvedic Kadha for prevention and management of the novel Coronavirus (SARS-CoV-2) using in silico approach

“…A number of Ayurvedic herbs have been used for management of SARS-CoV-2 infection (Shree et al, 2020 ; Tripathi et al, 2020 ). Some of the key Indian herbs such as Ashwagandha, Tulsi, Giloy and Turmeric contain several active phytochemicals which selectively bind with various SARS-CoV-2 vital targets (Chowdhury, 2020 ; Emirik, 2020 ; Kumar et al, 2020 ; Sen et al, 2020 ; Shree et al, 2020 ; Tripathi et al, 2020 ). The phytochemicals from several Indian spices have also shown possible beneficial effect against SARS-CoV-2 (Sen et al, 2020 ).…”

“…The Ministry of AYUSH (Ayurvedic, Yoga and Naturopathy, Unani, Siddha and Homeopathy), Government of India, has recommended the use of Kadha for boosting the immunity and reducing inflammation during COVID-19 crisis (The Ministry of AYUSH 2020). To manage COVID-19 crisis, several Indian Ayurvedic herbs, spices and their active phytochemicals have been explored for their possible prophylactic and therapeutic use against COVID-19 (Chowdhury, 2020 ; Emirik, 2020 ; Kumar et al, 2020 ; Sen et al, 2020 ; Shree et al, 2020 ; Swargiary et al, 2020 ; Tripathi et al, 2020 ).…”