Hordatines as a Potential Inhibitor of COVID-19 Main Protease and RNA Polymerase: An In-Silico Approach

Abstract

Total 40 natural compounds were selected to perform the molecular docking studies to screen and identify the potent antiviral agents specifically for Severe Acute Respiratory Syndrome Coronavirus 2 that causes coronavirus disease 2019 (COVID-19). The key targets of COVID-19, protease (PDB ID: 7BQY) and RNA polymerase (PDB ID: 7bV2) were used to dock our target compounds by Molecular Operating Environment (MOE) version 2014.09. We used 3 different conformations of protease target (6M0K, 6Y2F and 7BQY) and two different score functions to strengthen the probability of inhibitors discovery. After an extensive screening analysis, 20 compounds exhibit good binding affinities to one or both COVID-19 targets. 7 out of 20 compounds were predicted to overcome the activity of both targets. The top 7 hits are, flacourticin (3), sagerinic acid (16), hordatine A (23), hordatine B (24), N-feruloyl tyramine dimer (25), bisavenanthramides B-5 (29) and vulnibactins (40). According to our results, all these top hits was found to have a better binding scores than remdesivir, the native ligand in RNA polymerase target (PDB ID: 7bV2). Hordatines are phenolic compounds present in barley, were found to exhibit the highest binding affinity to both protease and polymerase through forming strong hydrogen bonds with the catalytic residues, as well as significant interactions with other receptor-binding residues. These results probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiment and accurate clinical trials are needed to confirm the preventive potentials of these compounds. Graphic Abstract

Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor

“…Different software tested the interaction between the tested compounds and the binding site through physics-based equations used to calculate their binding affinities (Sliwoski et al, 2014 ). SARS-CoV-2 proteins, particularly proteases and spike proteins (Prajapat et al, 2020 ), have been targeted in many docking investigations hoping to understand the key amino acids essential for the interactions at the active site in SARS-CoV-2 (Calligari et al, 2020 ; Dahab et al, 2020 ; Khan et al, 2020 ; Kumar et al, 2020 ; Mohammad et al, 2020 ; Wu et al, 2020 ; Jairajpuri et al, 2021 ).…”

Chemical Compound Identification of Two Varieties Cat of Whiskers (Orthosiphon aristatus Blume Miq) from In Vitro Culture

“…Rosmarinic acid compound, the main ingredient of O. aristatus based on in-silico studies, can inhibit COVID-19 (Sarkar and Das, 2020;Wondmkun and Mohammed, 2020;Sampangi-crowdedah et al, 2019). The potential of other compounds in O. aristatus as an inhibitor of COVID-19 is sinensetin, cirsimaritin, 1,8-cineole, sagerinic acid, caffeic acid derivatives, and β-caryophyllene (Rowaiye et al, 2020;Sekiou et al, 2020;Sharma and Kaur, 2020;Dahab et al, 2020;Adem et al, 2020;Narkhede et al, 2020). Other studies have reported the effects of sinensetin, caffeic acid, limonene, 1,8-cineol, eugenol, and aurantiamide compounds as anti-influenza viruses (Shin et al, 2012;Li et al, 2020;Utsunomiya et al, 2014;Nagy et al, 2018;Li et al, 2016;Choi, 2018;Dai et al, 2013;Zhou et al, 2017).…”

Isolasi Sinensetin dari Kumis Kucing (Orthosiphon aristatus Blume miq.) Varietas Putih

“…Pada masa pandemi Covid-19 penemuan senyawa atau tanaman obat tradisional yang berpotensi sebagai antivirus dan imunomodulator terus dilakukan dan berdasarkan hasil penelitian senyawa yang terkandung dalam tanaman kumis kucing berpotensi sebagai inhibitor Covid-19 (Sarkar & Das ;Rowaiye et al, 2020;Sekiou et al, 2020;Adem et al, 2020;Dahab et al, 2020;Narkhede et al, 2020;Sharma & Kaur, 2020;Faramayuda et al, 2021), antiherpetik (Ikeda et al, 2011;Medini et al, 2016;Astani et al, 2011;Astani & Schnitzler, 2014;Bourne et al, 1999;Benencia & Courreges, 2000;Sharifi-Rad et al, 2018), anti-human immunodeficiency virus (HIV) (Lin et al, 1999;McDougall et al, 1998;Zhang et al, 2014;Mengoni et al, 2002;Kashiwada et al, 1998;Xu et al, 1996), anti hepatitis (Haid et al, 2012;Duan et al, 2016;Kong et al, 2013;Chang et al, 2016) dan imunomodulator (Harun et al, 2015;Woottisin et al, 2011;Friedman, 2015;Kim et al, 2008;Takano et al, 2004;Sanbongi et al, 2004;Youn et al, 2003).…”