Mechanisms Underlying Potential Therapeutic Approaches for COVID-19

Benani, Abdelouaheb; Mkaddem, Sanae Ben

doi:10.3389/fimmu.2020.01841

Cited by 13 publications

(12 citation statements)

References 79 publications

(83 reference statements)

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“…1,2 There is no approved standard treatment, cure, or vaccine against COVID-19 and it is expected that both infections and mortalities will continue to rise globally. 3–5 The epicenter of the pandemic has moved from Wuhan, China, through Europe and is now in the United States of America where currently the highest number of infections and deaths is being reported (World Health Organization. 2 At all the epicenters, an initial slow infection rate was followed by a rapid exponential infection phase possibly associated with factors including socio-demographic profiles, host immune responses, and viral genetics.…”

Section: Introductionmentioning

confidence: 99%

Genomic analysis of SARS-CoV-2 reveals local viral evolution in Ghana

Ngoi

Quashie

Morang’a

et al. 2020

Exp Biol Med (Maywood)

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The confirmed case fatality rate for the coronavirus disease 2019 (COVID-19) in Ghana has dropped from a peak of 2% in March to be consistently below 1% since May 2020. Globally, case fatality rates have been linked to the strains/clades of circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a specific country. Here we present 46 whole genomes of SARS-CoV-2 circulating in Ghana, from two separate sequencing batches: 15 isolates from the early epidemic (March 12–April 1 2020) and 31 from later time-points ( 25–27 May 2020). Sequencing was carried out on an Illumina MiSeq system following an amplicon-based enrichment for SARS-CoV-2 cDNA. After genome assembly and quality control processes, phylogenetic analysis showed that the first batch of 15 genomes clustered into five clades: 19A, 19B, 20A, 20B, and 20C, whereas the second batch of 31 genomes clustered to only three clades 19B, 20A, and 20B. The imported cases (6/46) mapped to circulating viruses in their countries of origin, namely, India, Hungary, Norway, the United Kingdom, and the United States of America. All genomes mapped to the original Wuhan strain with high similarity (99.5–99.8%). All imported strains mapped to the European superclade A, whereas 5/9 locally infected individuals harbored the B4 clade, from the East Asian superclade B. Ghana appears to have 19B and 20B as the two largest circulating clades based on our sequence analyses. In line with global reports, the D614G linked viruses seem to be predominating. Comparison of Ghanaian SARS-CoV-2 genomes with global genomes indicates that Ghanaian strains have not diverged significantly from circulating strains commonly imported into Africa. The low level of diversity in our genomes may indicate lower levels of transmission, even for D614G viruses, which is consistent with the relatively low levels of infection reported in Ghana.

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Section: Introductionmentioning

confidence: 99%

Genomic analysis of SARS-CoV-2 reveals local viral evolution in Ghana

Ngoi

Quashie

Morang’a

et al. 2020

Exp Biol Med (Maywood)

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“…There is a pressing demand for the anti-COVID-19 drugs. Researchers across the globe are looking for strategies to block the interaction of RBD with ACE2[ [6] , [7] , [8] , [9] , [10] ]. Pharmaceutical companies such as Moderna and AstraZeneca have invented vaccines that are based on the genetic sequence of spike protein[ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Drug repurposing against SARS-CoV-2 receptor binding domain using ensemble-based virtual screening and molecular dynamics simulations

Kumar

Liu

2021

Computers in Biology and Medicine

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused worldwide pandemic and is responsible for millions of worldwide deaths due to -a respiratory disease known as COVID-19. In the search for a cure of COVID-19, drug repurposing is a fast and cost-effective approach to identify anti-COVID-19 drugs from existing drugs. The receptor binding domain (RBD) of the SARS-CoV-2 spike protein has been a main target for drug designs to block spike protein binding to ACE2 proteins. In this study, we probed the conformational plasticity of the RBD using long molecular dynamics (MD) simulations, from which, representative conformations were identified using clustering analysis. Three simulated conformations and the original crystal structure were used to screen FDA approved drugs (2466 drugs) against the predicted binding site at the ACE2-RBD interface, leading to 18 drugs with top docking scores. Notably, 16 out of the 18 drugs were obtained from the simulated conformations, while the crystal structure suggests poor binding. The binding stability of the 18 drugs were further investigated using MD simulations. Encouragingly, 6 drugs exhibited stable binding with RBD at the ACE2-RBD interface and 3 of them (gonadorelin, fondaparinux and atorvastatin) showed significantly enhanced binding after the MD simulations. Our study shows that flexibility modeling of SARS-CoV-2 RBD using MD simulation is of great help in identifying novel agents which might block the interaction between human ACE2 and the SARS-CoV-2 RBD for inhibiting the virus infection.

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“…Parallelly, the collective scientific community has been trying to explore and target the key proteins of SARS-CoV-2 mutant’s pathogenesis including after infection human immuno-pathophysiology. Subsequently, a lot of data has been reported in terms of review articles that describe hosts responses, clinical features, proposed treatment interventions and their mechanism of action (MOA) associated with SARS-CoV-2 infection or COVID-19 [1] , [2] , [3] , [4] , [5] , [6] , [7] . Nevertheless, research on SARS-CoV-2 and COVID-19 is progressing with time in terms of rational design of novel drugs, natural products drug discovery, immuno-pathological and clinical outcomes based on host nutritional, metabolic and lifestyle status, role of herbo-mineral formulations in innate/adaptive immunity modulation to contain the disease.…”

Section: Introductionmentioning

confidence: 99%