EXCLI J. Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: An in silico analysis

[tetano]

EXCLI J. 2020 Mar 18;19:410-417. doi: 10.17179/excli2020-1167. eCollection 2020.
Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: An in silico analysis.


Ortega JT¹, Serrano ML², Pujol FH³, Rangel HR³.

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Abstract

Many human viral diseases are a consequence of a zoonotic event. Some of the diseases caused by these zoonotic events have affected millions of people around the world, some of which have resulted in high rates of morbidity/mortality in humans. Changes in the viral proteins that function as ligands of the host receptor may promote the spillover between species. The most recent of these zoonotic events that have caused an ongoing epidemic of high magnitude is the Covid-19 epidemics caused by SARS-CoV-2. The aim of this study was to determine the mutation(s) in the sequence of the spike protein of the SARS-CoV-2 that might be favoring human to human transmission. An in silico approach was performed, and changes were detected in the S1 subunit of the receptor-binding domain of spike. The observed changes have significant effect on SARS-CoV-2 spike/ACE2 interaction and produce a reduction in the binding energy, compared to the one of the Bat-CoV to this receptor. The data presented in this study suggest a higher affinity of the SARS-Cov-2 spike protein to the human ACE2 receptor, compared to the one of Bat-CoV spike and ACE2. This could be the cause of the rapid viral spread of SARS-CoV-2 in humans.
Copyright ? 2020 Ortega et al.



KEYWORDS:

ACE2; Coronavirus; SARS-CoV-2; Spike; outbreak


PMID:32210742PMCID:PMC7081066DOI:10.17179/excli2020-1167

[tetano]

EXCLI J. 2020 Mar 17;19:400-409. doi: 10.17179/excli2020-1189. eCollection 2020.
Unrevealing sequence and structural features of novel coronavirus using in silico approaches: The main protease as molecular target.


Ortega JT¹, Serrano ML², Pujol FH³, Rangel HR³.

Author information




Abstract

Direct-acting antivirals are effective tools to control viral infections. SARS-CoV-2 is a coronavirus associated with the epidemiological outbreak in late 2019. Previous reports showed that HIV-1 protease inhibitors could block SARS-CoV main protease. Based on that and using an in silico approach, we evaluated SARS-CoV-2 main protease as a target for HIV-1 protease inhibitors to reveal the structural features related to their antiviral effect. Our results showed that several HIV inhibitors such as lopinavir, ritonavir, and saquinavir produce strong interaction with the active site of SARS-CoV-2 main protease. Furthermore, broad library protease inhibitors obtained from PubChem and ZINC (www.zinc.docking.org) were evaluated. Our analysis revealed 20 compounds that could be clustered into three groups based on their chemical features. Then, these structures could serve as leading compounds to develop a series of derivatives optimizing their activity against SARS-CoV-2 and other coronaviruses. Altogether, the results presented in this work contribute to gain a deep understanding of the molecular pharmacology of SARS-CoV-2 treatment and validate the use of protease inhibitors against SARS-CoV-2.
Copyright ? 2020 Ortega et al.



KEYWORDS:

Coronavirus; HIV; SARS-CoV-2; protease; treatment


PMID:32210741PMCID:PMC7081067DOI:10.17179/excli2020-1189