tetano
Editor, Senior Moderator
Heliyon
. 2021 Mar;7(3):e06435.
doi: 10.1016/j.heliyon.2021.e06435. Epub 2021 Mar 5.
Structural analogues of existing anti-viral drugs inhibit SARS-CoV-2 RNA dependent RNA polymerase: A computational hierarchical investigation
Md Kamrul Hasan[SUP] 1 [/SUP], Mohammad Kamruzzaman[SUP] 2 [/SUP], Omar Hamza Bin Manjur[SUP] 2 [/SUP], Araf Mahmud[SUP] 3 [/SUP], Nazmul Hussain[SUP] 1 [/SUP], Muhammad Shafiul Alam Mondal[SUP] 2 [/SUP], Md Ismail Hosen[SUP] 2 [/SUP], Martiniano Bello[SUP] 4 [/SUP], Atiqur Rahman[SUP] 2 [/SUP]
Affiliations
Abstract
The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a pandemic, resulting in an exponentially increased mortality globally and scientists all over the world are struggling to find suitable solutions to combat it. Multiple repurposed drugs have already been in several clinical trials or recently completed. However, none of them shows any promising effect in combating COVID-19. Therefore, developing an effective drug is an unmet global need. RdRp (RNA dependent RNA polymerase) plays a pivotal role in viral replication. Therefore, it is considered as a prime target of drugs that may treat COVID-19. In this study, we have screened a library of compounds, containing approved RdRp inhibitor drugs that were or in use to treat other viruses (favipiravir, sofosbuvir, ribavirin, lopinavir, tenofovir, ritonavir, galidesivir and remdesivir) and their structural analogues, in order to identify potential inhibitors of SARS-CoV-2 RdRp. Extensive screening, molecular docking and molecular dynamics show that five structural analogues have notable inhibitory effects against RdRp of SARS-CoV-2. Importantly, comparative protein-antagonists interaction revealed that these compounds fit well in the pocket of RdRp. ADMET analysis of these compounds suggests their potency as drug candidates. Our identified compounds may serve as potential therapeutics for COVID-19.
Keywords: Binding free energy; COVID-19; Molecular docking; Molecular dynamics simulation; RNA dependent RNA polymerase; Virtual screening.
. 2021 Mar;7(3):e06435.
doi: 10.1016/j.heliyon.2021.e06435. Epub 2021 Mar 5.
Structural analogues of existing anti-viral drugs inhibit SARS-CoV-2 RNA dependent RNA polymerase: A computational hierarchical investigation
Md Kamrul Hasan[SUP] 1 [/SUP], Mohammad Kamruzzaman[SUP] 2 [/SUP], Omar Hamza Bin Manjur[SUP] 2 [/SUP], Araf Mahmud[SUP] 3 [/SUP], Nazmul Hussain[SUP] 1 [/SUP], Muhammad Shafiul Alam Mondal[SUP] 2 [/SUP], Md Ismail Hosen[SUP] 2 [/SUP], Martiniano Bello[SUP] 4 [/SUP], Atiqur Rahman[SUP] 2 [/SUP]
Affiliations
- PMID: 33693066
- PMCID: PMC7934700
- DOI: 10.1016/j.heliyon.2021.e06435
Abstract
The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a pandemic, resulting in an exponentially increased mortality globally and scientists all over the world are struggling to find suitable solutions to combat it. Multiple repurposed drugs have already been in several clinical trials or recently completed. However, none of them shows any promising effect in combating COVID-19. Therefore, developing an effective drug is an unmet global need. RdRp (RNA dependent RNA polymerase) plays a pivotal role in viral replication. Therefore, it is considered as a prime target of drugs that may treat COVID-19. In this study, we have screened a library of compounds, containing approved RdRp inhibitor drugs that were or in use to treat other viruses (favipiravir, sofosbuvir, ribavirin, lopinavir, tenofovir, ritonavir, galidesivir and remdesivir) and their structural analogues, in order to identify potential inhibitors of SARS-CoV-2 RdRp. Extensive screening, molecular docking and molecular dynamics show that five structural analogues have notable inhibitory effects against RdRp of SARS-CoV-2. Importantly, comparative protein-antagonists interaction revealed that these compounds fit well in the pocket of RdRp. ADMET analysis of these compounds suggests their potency as drug candidates. Our identified compounds may serve as potential therapeutics for COVID-19.
Keywords: Binding free energy; COVID-19; Molecular docking; Molecular dynamics simulation; RNA dependent RNA polymerase; Virtual screening.