Yousery E Sherif1, Sami A Gabr2,3, Nasser M Hosny4, Ahmad H Alghadir2, Rayan Alansari5. 1. Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 2. Rehabilitation Research Chair, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia. 3. Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 4. Chemistry Department, Faculty of Science, Port Said University, Port Fuad, P O Box 42522, Egypt. 5. Biology Department, Al-Ula Branch, Taibah University, Medina, Saudi Arabia.
Abstract
BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) induced by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in China and spread to cover the entire world with an ongoing pandemic. The magnitude of the situation and the fast spread of the new and deadly virus, as well as the lack of specific treatment, led to a focus on research to discover new therapeutic agents. AIM: In this study, we explore the potential inhibitory effects of some active polyphenolic constituents of Rhus spp. (sumac) against the SARS-CoV-2 main protease enzyme (Mpro; 6LU7). METHODS: 26 active polyphenolic compounds of Rhus spp. were studied for their antiviral activity by molecular docking, drug likeness, and synthetic accessibility score (SAS) as inhibitors against the SARS-CoV-2 Mpro. RESULTS: The results show that all tested compounds of sumac provided good interaction with the main active site of SARS-CoV-2 Mpro, with better, lower molecular docking energy (kcal/mol) compared to the well-known drugs chloroquine and favipiravir (Avigan). Only six active polyphenolic compounds of Rhus spp. (sumac), methyl 3,4,5-trihydroxybenzoate, (Z)-1-(2,4-dihydroxyphenyl)-3-(3,4-dihydroxyphenyl)-2-hydroxyprop-2-en-1-one, (Z)-2-(3,4-dihydroxybenzylidene)-6-hydroxybenzofuran-3(2H)-one, 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chroman-4-one, 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4H-chroman-4-one, and 3,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one, were proposed by drug likeness, solubility in water, and SAS analysis as potential inhibitors of Mpro that may be used for the treatment of COVID-19. CONCLUSION: Six phenolic compounds of Rhus spp. are proposed for synthesis as potential inhibitors against Mpro and have potential for the treatment of COVID-19. These results encourage further in vitro and in vivo investigations of the proposed ligands and research on the preventive use of Rhus spp. against SARS-CoV-2.
BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) induced by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in China and spread to cover the entire world with an ongoing pandemic. The magnitude of the situation and the fast spread of the new and deadly virus, as well as the lack of specific treatment, led to a focus on research to discover new therapeutic agents. AIM: In this study, we explore the potential inhibitory effects of some active polyphenolic constituents of Rhus spp. (sumac) against the SARS-CoV-2 main protease enzyme (Mpro; 6LU7). METHODS: 26 active polyphenolic compounds of Rhus spp. were studied for their antiviral activity by molecular docking, drug likeness, and synthetic accessibility score (SAS) as inhibitors against the SARS-CoV-2 Mpro. RESULTS: The results show that all tested compounds of sumac provided good interaction with the main active site of SARS-CoV-2 Mpro, with better, lower molecular docking energy (kcal/mol) compared to the well-known drugs chloroquine and favipiravir (Avigan). Only six active polyphenolic compounds of Rhus spp. (sumac), methyl 3,4,5-trihydroxybenzoate, (Z)-1-(2,4-dihydroxyphenyl)-3-(3,4-dihydroxyphenyl)-2-hydroxyprop-2-en-1-one, (Z)-2-(3,4-dihydroxybenzylidene)-6-hydroxybenzofuran-3(2H)-one, 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chroman-4-one, 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4H-chroman-4-one, and 3,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one, were proposed by drug likeness, solubility in water, and SAS analysis as potential inhibitors of Mpro that may be used for the treatment of COVID-19. CONCLUSION: Six phenolic compounds of Rhus spp. are proposed for synthesis as potential inhibitors against Mpro and have potential for the treatment of COVID-19. These results encourage further in vitro and in vivo investigations of the proposed ligands and research on the preventive use of Rhus spp. against SARS-CoV-2.
Authors: Y M Lin; H Anderson; M T Flavin; Y H Pai; E Mata-Greenwood; T Pengsuparp; J M Pezzuto; R F Schinazi; S H Hughes; F C Chen Journal: J Nat Prod Date: 1997-09 Impact factor: 4.050
Authors: M Kurokawa; T Hozumi; P Basnet; M Nakano; S Kadota; T Namba; T Kawana; K Shiraki Journal: J Pharmacol Exp Ther Date: 1998-02 Impact factor: 4.030
Authors: Yashodhara Dasgupta; Konstantin Golovine; Margaret Nieborowska-Skorska; Li Luo; Ksenia Matlawska-Wasowska; Charles G Mullighan; Tomasz Skorski Journal: Leuk Lymphoma Date: 2017-11-08
Authors: David S Hui; Esam I Azhar; Tariq A Madani; Francine Ntoumi; Richard Kock; Osman Dar; Giuseppe Ippolito; Timothy D Mchugh; Ziad A Memish; Christian Drosten; Alimuddin Zumla; Eskild Petersen Journal: Int J Infect Dis Date: 2020-01-14 Impact factor: 3.623