tetano
Editor, Senior Moderator
Medicina (Kaunas)
. 2021 Dec 23;58(1):20.
doi: 10.3390/medicina58010020.
Potential Role of Colchicine in Combating COVID-19 Cytokine Storm and Its Ability to Inhibit Protease Enzyme of SARS-CoV-2 as Conferred by Molecular Docking Analysis
Noha A Kamel[SUP] 1 [/SUP], Nasser S M Ismail[SUP] 2 [/SUP], Ibrahim S Yahia[SUP] 3 4 5 [/SUP], Khaled M Aboshanab[SUP] 6 [/SUP]
Affiliations
Abstract
Despite the advance in the management of Coronavirus disease 2019 (COVID-19), the global pandemic is still ongoing with a massive health crisis. COVID-19 manifestations may range from mild symptoms to severe life threatening ones. The hallmark of the disease severity is related to the overproduction of pro-inflammatory cytokines manifested as a cytokine storm. Based on its anti-inflammatory activity through interfering with several pro and anti-inflammatory pathways, colchicine had been proposed to reduce the cytokine storm and subsequently improve clinical outcomes. Molecular docking analysis of colchicine against RNA-dependent RNA polymerase (RdRp) and protease enzymes of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) revealed that colchicine provided a grid-based molecular docking method, C-DOCKER interaction energy 64.26 and 47.53 (Kcal/mol) with protease and RdRp, respectively. This finding indicated higher binding stability for colchicine-protease complexes than the colchicine-RdRp complex with the involvement of seven hydrogen bonds, six hydrogen acceptors with Asn142, Gly143, Ser144, and Glu166 and one hydrogen-bond donors with Cys145 of the protease enzyme. This is in addition to three hydrophobic interactions with His172, Glu166, and Arg188. A good alignment with the reference compound, Boceprevir, indicated high probability of binding to the protease enzyme of SARS-CoV-2. In conclusion, colchicine can ameliorate the destructive effect of the COVID-19 cytokine storm with a strong evidence of antiviral activity by inhibiting the protease enzyme of SARS-CoV-2.
Keywords: COVID-19; RNA polymerase; SARS-CoV-2; colchicine; cytokine storm; molecular docking; protease inhibitor.
. 2021 Dec 23;58(1):20.
doi: 10.3390/medicina58010020.
Potential Role of Colchicine in Combating COVID-19 Cytokine Storm and Its Ability to Inhibit Protease Enzyme of SARS-CoV-2 as Conferred by Molecular Docking Analysis
Noha A Kamel[SUP] 1 [/SUP], Nasser S M Ismail[SUP] 2 [/SUP], Ibrahim S Yahia[SUP] 3 4 5 [/SUP], Khaled M Aboshanab[SUP] 6 [/SUP]
Affiliations
- PMID: 35056328
- DOI: 10.3390/medicina58010020
Abstract
Despite the advance in the management of Coronavirus disease 2019 (COVID-19), the global pandemic is still ongoing with a massive health crisis. COVID-19 manifestations may range from mild symptoms to severe life threatening ones. The hallmark of the disease severity is related to the overproduction of pro-inflammatory cytokines manifested as a cytokine storm. Based on its anti-inflammatory activity through interfering with several pro and anti-inflammatory pathways, colchicine had been proposed to reduce the cytokine storm and subsequently improve clinical outcomes. Molecular docking analysis of colchicine against RNA-dependent RNA polymerase (RdRp) and protease enzymes of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) revealed that colchicine provided a grid-based molecular docking method, C-DOCKER interaction energy 64.26 and 47.53 (Kcal/mol) with protease and RdRp, respectively. This finding indicated higher binding stability for colchicine-protease complexes than the colchicine-RdRp complex with the involvement of seven hydrogen bonds, six hydrogen acceptors with Asn142, Gly143, Ser144, and Glu166 and one hydrogen-bond donors with Cys145 of the protease enzyme. This is in addition to three hydrophobic interactions with His172, Glu166, and Arg188. A good alignment with the reference compound, Boceprevir, indicated high probability of binding to the protease enzyme of SARS-CoV-2. In conclusion, colchicine can ameliorate the destructive effect of the COVID-19 cytokine storm with a strong evidence of antiviral activity by inhibiting the protease enzyme of SARS-CoV-2.
Keywords: COVID-19; RNA polymerase; SARS-CoV-2; colchicine; cytokine storm; molecular docking; protease inhibitor.