Structural basis for the inhibition of SARS-CoV2 main protease by Indian medicinal plant-derived antiviral compounds

Abstract

A novel coronavirus (SARS-CoV2) has caused a major outbreak in humans around the globe, and it became a severe threat to human healthcare than all other infectious diseases. Researchers were urged to discover and test various approaches to control and prevent such a deadly disease. Considering the emergency and necessity, we screened reported antiviral compounds present in the traditional Indian medicinal plants for the inhibition of SARS-CoV2 main protease. In this study, we used molecular docking to screen 41 reported antiviral compounds that exist in Indian medicinal plants and shown amentoflavone from the plant Torreyanucifera with a higher docking score. Furthermore, we performed a 40 ns atomic molecular dynamics simulation and free binding energy calculations to explore the stability of the top five protein–ligand complexes. Through the article, we insist that the amentoflavone, hypericin and Torvoside H from the traditional Indian medicinal plants may be used as a potential inhibitor of SARS-CoV2 main protease and further biochemical experiments could shed light on understanding the mechanism of inhibition by these plant-derived antiviral compounds. Communicated by Ramaswamy H. Sarma

Combined use of the hepatitis C drugs and amentoflavone could interfere with binding of the spike glycoprotein of SARS-CoV-2 to ACE2: the results of a molecular simulation study

“…To the best of our knowledge, there are no other MD simulations of paritaprevir–RBD and amentoflavone–RBD complexes. But, there are many stable MD simulations of the amentoflavone complex with the main protease (Ghosh et al, 2020 ; Lokhande et al, 2020 ; Mishra et al, 2020 ; Patil et al, 2021 ; Saravanan et al, 2020 ; Swargiary et al, 2020 ). For paritaprevir and simeprevir, stable MD simulations with the main protease and the uridylate-specific endoribonuclease (NSP15) have been obtained (Alamri et al, 2020 ; Khan, Jha, Amera, et al, 2020 ; Khan, Jha, Singh, et al, 2020 ).…”

“…Besides, amentoflavone is an effective inhibitor (IC 50 ¼ 8.3 mM) of the SARS-CoV main protease (Ryu et al, 2010). In the recent in silico studies (Ghosh et al, 2020;Lokhande et al, 2020;Mishra et al, 2020;Patil et al, 2021;Peterson, 2020;Puttaswamy et al, 2020;Saravanan et al, 2020;Swargiary et al, 2020), amentoflavone has been reported to bind tightly to the main protease of SARS-CoV-2. There are also three docking studies targeting spike glycoprotein of SARS-CoV-2, in which amentoflavone was found among the hit compounds with the binding energies: À7.6 kcal/mol (Wei et al, 2020), À8.7 kcal/mol (Puttaswamy et al, 2020), and À10.2 kcal/mol (Rameshkumar et al, 2021).…”

“…Most of the molecular modeling studies against SARS-CoV-2 use the main protease as a drug target (Aanouz et al, 2020;Alamri et al, 2020;Badavath et al, 2020;Bhardwaj et al, 2020Bhardwaj et al, , 2021Ghosh et al, 2020;Jim enez-Alberto et al, 2020;Khan, Ali, et al, 2020;Kumar et al, 2020;Lokhande et al, 2020;Mishra et al, 2020;Saravanan et al, 2020). Perhaps this is because of the pivotal role of this enzyme in the virus life cycle and the high conservation of its active site (Ullrich & Nitsche, 2020).…”

An Overview on Antiviral Potential of Traditional Medicines

“…Furthermore, free energy calculations on these compounds performed by using the molecular docking procedure. The results suggested that amentaflavone, hypericin, and Torvoside H respectively complexed with SARS-CoV-2 Mpro show better binding with stabilizing interactions and provided valuable information in developing new, novel and natural anti-viral drugs for COVID-19 [9]. In addition, taraxerol isolated from Clerodendrum species has shown potential antiviral activities with desirable pharmacological features [12].…”

“…It has been shown that Coptidis rhizome, Meliae cortex, Sanguisorbae radix, Cimicifuga rhizome, and Phellodendron cortex exhibit anti-coronavirus activity. Sophorae radix, Tor ilis fructus, and Acanthopanacis cortex decreased intracellular viral RNA levels with corresponding viral protein decreases [9]. The antiviral activity of some phytoconstituents present in traditional medicinal plants from Ayurveda were also investigated against spike glycoprotein of SARS-COV-2 as well as its host ACE-2 receptor.…”