In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19

Kumar, Vipul; Jena, Manoj Kumar

doi:10.21203/rs.3.rs-31775/v1

Cited by 15 publications

(10 citation statements)

References 36 publications

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“…Phensuximide was found in molecular docking simulations of FDA-approved small compounds associated with protection against COVID-19, M pro [ 35 ]. In VS-based study, magnesium ascorbate, a buffered (non-acidic) form of vitamin C, was found to be the top lead compound among 106 nutraceuticals against SARS-CoV-2 s M pro [ 36 ], and tizanidine was amongst the 11 approved drugs predicted to show a high binding affinity in VS study with M pro [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel In Silico Method

et al. 2020

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The SARS-CoV-2 outbreak caused an unprecedented global public health threat, having a high transmission rate with currently no drugs or vaccines approved. An alternative powerful additional approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 main protease is essential for viral replication and an attractive drug target. In this study, we used the virtual screening protocol with both long-range and short-range interactions to select candidate SARS-CoV-2 main protease inhibitors. First, the Informational spectrum method applied for small molecules was used for searching the Drugbank database and further followed by molecular docking. After in silico screening of drug space, we identified 57 drugs as potential SARS-CoV-2 main protease inhibitors that we propose for further experimental testing.

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Section: Discussionmentioning

confidence: 99%

Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel In Silico Method

et al. 2020

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“…An inhibitory interaction between folic acid and the proteolytic protein furin, which was documented to promote activation of the coronavirus, was recently demonstrated [ 33 , 34 ]. Additionally, folic acid and its derivatives were found to have a direct anti-SARS-CoV−2 effect [ 35 , 36 ]. Singh et al proposed the incorporation of folic acid in the treatment regimen of COVID-19 [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Folate Levels in Patients Hospitalized with Coronavirus Disease 2019

et al. 2021

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We aimed to investigate the prevalence of decreased folate levels in patients hospitalized with Coronavirus Disease 2019 (COVID-19) and evaluate their outcome and the prognostic signifi-cance associated with its different levels. In this retrospective cohort study, data were obtained from the electronic medical records at the Sheba Medical Center. Folic acid levels were available in 333 out of 1020 consecutive patients diagnosed with COVID-19 infection hospitalized from January 2020 to November 2020. Thirty-eight (11.4%) of the 333 patients comprising the present study population had low folate levels. No significant difference was found in the incidence of acute kidney injury, hypoxemia, invasive ventilation, length of hospital stay, and mortality be-tween patients with decreased and normal-range folate levels. When sub-dividing the study population according to quartiles of folate levels, similar findings were observed. In conclusion, decreased serum folate levels are common among hospitalized patients with COVID-19, but there was no association between serum folate levels and clinical outcomes. Due to the important role of folate in cell metabolism and the potential pathologic impact when deficient, a follow-up of folate levels or possible supplementation should be encouraged in hospitalized COVID-19 patients. Fur-ther studies are required to assess the prevalence and consequences of folate deficiency in COVID-19 patients.

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“…Sapropterin (14.33% inhibition), a phenylalanine-4-hydroxylase stimulant and tetrahydrofolic acid (28.84% inhibition) were also confirmed in vitro to be SARS-CoV-2 inhibitors. Folic acid and its derivatives (tetrahydrofolic acid and 5-methyl tetrahydrofolic acid) have been reported to have good binding affinity to viral proteins in various VS studies (Kumar & Jena, 2020 ). The second pharmacophore search based on the U5P ligand resulted in uridine-5-triphosphate, baicalin, cyclic-AMP, INS316, adenosine phosphate and diadenosine tetraphosphate.…”

Section: Discussionmentioning

confidence: 99%

Repurposing drugs for treatment of SARS-CoV-2 infection: computational design insights into mechanisms of action

Kandwal

Fayne

2020

Journal of Biomolecular Structure and Dynamics

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The COVID-19 pandemic has negatively affected human life globally. It has led to economic crises and health emergencies across the world, spreading rapidly among the human population and has caused many deaths. Currently, there are no treatments available for COVID-19 so there is an urgent need to develop therapeutic interventions that could be used against the novel coronavirus infection. In this research, we used computational drug design technologies to repurpose existing drugs as inhibitors of SARS-CoV-2 viral proteins. The Broad Institute's Drug Repurposing Hub consists of in-development/ approved drugs and was computationally screened to identify potential hits which could inhibit protein targets encoded by the SARS-CoV-2 genome. By virtually screening the Broad collection, using rationally designed pharmacophore features, we identified molecules which may be repurposed against viral nucleocapsid and non-structural proteins. The pharmacophore features were generated after careful visualisation of the interactions between co-crystalised ligands and the protein binding site. The ChEMBL database was used to determine the compound's level of inhibition of SARS-CoV-2 and correlate the predicted viral protein target with whole virus in vitro data. The results from this study may help to accelerate drug development against COVID-19 and the hit compounds should be progressed through further in vitro and in vivo studies on SARS-CoV-2.

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In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19

Cited by 15 publications

References 36 publications

Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel In Silico Method

Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel In Silico Method

Folate Levels in Patients Hospitalized with Coronavirus Disease 2019

Repurposing drugs for treatment of SARS-CoV-2 infection: computational design insights into mechanisms of action

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