tetano
Editor, Senior Moderator
Molecules
. 2021 Jan 28;26(3):673.
doi: 10.3390/molecules26030673.
Chloroquine and Hydroxychloroquine Interact Differently with ACE2 Domains Reported to Bind with the Coronavirus Spike Protein: Mediation by ACE2 Polymorphism
Riadh Badraoui[SUP] 1 2 3 [/SUP], Mohd Adnan[SUP] 1 [/SUP], Fevzi Bardakci[SUP] 1 4 [/SUP], Mousa M Alreshidi[SUP] 1 5 [/SUP]
Affiliations
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection inducing coronavirus disease 2019 (COVID-19) is still an ongoing challenge. To date, more than 95.4 million have been infected and more than two million deaths have been officially reported by the WHO. Angiotensin-converting enzyme (ACE) plays a key role in the disease pathogenesis. In this computational study, seventeen coding variants were found to be important for ACE2 binding with the coronavirus spike protein. The frequencies of these allele variants range from 3.88 ? 10[SUP]-3[/SUP] to 5.47 ? 10[SUP]-6[/SUP] for rs4646116 (K26R) and rs1238146879 (P426A), respectively. Chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are mainly used to prevent and treat malaria and rheumatic diseases. They are also used in several countries to treat SARS-CoV-2 infection inducing COVID-19. Both CQ and HCQ were found to interact differently with the various ACE2 domains reported to bind with coronavirus spike protein. A molecular docking approach revealed that intermolecular interactions of both CQ and HCQ exhibited mediation by ACE2 polymorphism. Further explorations of the relationship and the interactions between ACE2 polymorphism and CQ/HCQ would certainly help to better understand the COVID-19 management strategies, particularly their use in the absence of specific vaccines or drugs.
Keywords: ACE2 allelic variants; binding domain; chloroquine; coronavirus; hydroxychloroquine; in silico; molecular docking; molecular interactions.
. 2021 Jan 28;26(3):673.
doi: 10.3390/molecules26030673.
Chloroquine and Hydroxychloroquine Interact Differently with ACE2 Domains Reported to Bind with the Coronavirus Spike Protein: Mediation by ACE2 Polymorphism
Riadh Badraoui[SUP] 1 2 3 [/SUP], Mohd Adnan[SUP] 1 [/SUP], Fevzi Bardakci[SUP] 1 4 [/SUP], Mousa M Alreshidi[SUP] 1 5 [/SUP]
Affiliations
- PMID: 33525415
- DOI: 10.3390/molecules26030673
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection inducing coronavirus disease 2019 (COVID-19) is still an ongoing challenge. To date, more than 95.4 million have been infected and more than two million deaths have been officially reported by the WHO. Angiotensin-converting enzyme (ACE) plays a key role in the disease pathogenesis. In this computational study, seventeen coding variants were found to be important for ACE2 binding with the coronavirus spike protein. The frequencies of these allele variants range from 3.88 ? 10[SUP]-3[/SUP] to 5.47 ? 10[SUP]-6[/SUP] for rs4646116 (K26R) and rs1238146879 (P426A), respectively. Chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are mainly used to prevent and treat malaria and rheumatic diseases. They are also used in several countries to treat SARS-CoV-2 infection inducing COVID-19. Both CQ and HCQ were found to interact differently with the various ACE2 domains reported to bind with coronavirus spike protein. A molecular docking approach revealed that intermolecular interactions of both CQ and HCQ exhibited mediation by ACE2 polymorphism. Further explorations of the relationship and the interactions between ACE2 polymorphism and CQ/HCQ would certainly help to better understand the COVID-19 management strategies, particularly their use in the absence of specific vaccines or drugs.
Keywords: ACE2 allelic variants; binding domain; chloroquine; coronavirus; hydroxychloroquine; in silico; molecular docking; molecular interactions.