In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19
Vipul Kumar, Sudhakar Kancharla, Manoj Kumar
The recent outbreak of the novel coronavirus (SARS-CoV-2) in the Wuhan province of China has taken millions of lives worldwide. In this pandemic situation and absence of known drugs and vaccines against novel coronavirus disease (COVID-19), there is an urgent need for the repurposing of the existing drugs against it. So, here we have examined a safe and cheap alternative against this virus by screening hundreds of nutraceuticals compounds against known therapeutic targets of SARS-COV-2 by molecular docking. The virtual screening results were then analyzed for binding energy and interactive residues and compared with some already known hits in the best binding pose. All these analyses of this study strongly predicted the potential of Folic acid and its derivates like Tetrahydrofolic acid and 5-methyl tetrahydrofolic acid against SARS-COV-2. The strong and stable binding affinity of this water-soluble vitamin and its derivatives against the SARS-COV-2, indicating that they could be valuable drugs against the management of this COVID-19 pandemic. This study could serve as the starting point for further investigation of these molecules through in vitro and in vivo assays.
References
Annunziata, Resveratrol as a novel anti-herpes simplex virus nutraceutical agent: an overview, Viruses,
doi:10.3390/v10090473
Bertram, Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease, J Virol,
doi:10.1128/JVI.05300-11
Bhardwaj, The coronavirus endoribonuclease Nsp15 interacts with retinoblastoma tumor suppressor protein, J Virol,
doi:10.1128/JVI.07012-11
Biovia, Discovery studio modeling environment
Chandra, Identification of potential inhibitors of SARS-COV-2 endoribonuclease (EndoU) from FDA approved drugs: a drug repurposing approach to find therapeutics for COVID-19, J Biomol Struct Dyn,
doi:10.1080/07391102.2020.1775127
Chase, Semler, Viral subversion of host functions for picornavirus translation and RNA replication, Future Virol,
doi:10.2217/fvl.12.2
Chen, Yu, First two months of the 2019 Coronavirus Disease (COVID-19) epidemic in China: real-time surveillance and evaluation with a second derivative model, Glob Health Res Policy,
doi:10.1186/s41256-020-00137-4
Daina, Michielin, Zoete, SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci Rep,
doi:10.1038/srep42717
Du, The spike protein of SARS-CoV-a target for vaccine and therapeutic development, Nat Rev Microbiol,
doi:10.1038/nrmicro2090
Feng, COVID-19 and liver dysfunction: current insights and emergent therapeutic strategies, J Clin Transl Hepatol,
doi:10.14218/jcth.2020.00018
Ghose, Viswanadhan, Wendoloski, A knowledgebased approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases, J Comb Chem,
doi:10.1021/cc9800071
Gorton, Jarvis, The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections, J Manip Physiol Ther,
doi:10.1016/s0161-4754(99)70005-9
Hoffmann, SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell,
doi:10.1016/j.cell.2020.02.052
Kim, Crystal structure of Nsp15 endoribonuclease Nen-doU from SARS-CoV-2, Protein Sci,
doi:10.1002/pro.3873
Kim, Vitamin C is an essential factor on the anti-viral immune responses through the production of interferon-alpha/beta at the initial stage of influenza a virus (H3N2) infection, Immune Netw,
doi:10.4110/in.2013.13.2.70
Kolifarhood, Epidemiological and clinical aspects of COVID-19; a narrative review, Arch Acad Emerg Med
Lipinski, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv Drug Deliv Rev,
doi:10.1016/s0169-409x(00)00129-0
Lu, Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding, Lancet,
doi:10.1016/S0140-6736(20)30251-8
Nasri, New concepts in nutraceuticals as alternative for pharmaceuticals, Int J Prev Med
Nichols, Campbell, Boeckh, Respiratory viruses other than influenza virus: impact and therapeutic advances, Clin Microbiol Rev,
doi:10.1128/cmr.00045-07
Ortiz-Alcantara, Bhardwaj, Palaninathan, Frieman, Baric et al., Small molecule inhibitors of the SARS-CoV Nsp15 endoribonuclease. Virus Adapt Treat Virus Adapt Treat
Ricagno, Crystal structure and mechanistic determinants of SARS coronavirus nonstructural protein 15 define an endoribonuclease family, Proc Natl Acad Sci,
doi:10.1073/pnas.0601708103
Rimanshee, Potential inhibitors against papain-like protease of novel coronavirus (SARS-CoV-2) from FDA approved drugs
Trott, Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J Comput Chem,
doi:10.1002/jcc.21334
Tyrrell, Myint, Coronaviruses
Van Woensel, Van Aalderen, Kimpen, Viral lower respiratory tract infection in infants and young children, BMJ,
doi:10.1136/bmj.327.7405.36
Vatansever, Targeting the SARS-CoV-2 main protease to repurpose drugs for COVID-19
Velthuis, The RNA polymerase activity of SARScoronavirus nsp12 is primer dependent, Nucl Acids Res,
doi:10.1093/nar/gkp904
Xu, Arbidol/IFN-alpha2b therapy for patients with corona virus disease 2019: a retrospective multicenter cohort study, Microbes Infect,
doi:10.1016/j.micinf.2020.05.012
Yamshchikov, Vitamin D for treatment and prevention of infectious diseases: a systematic review of randomized controlled trials, Endocr Pract,
doi:10.4158/EP09101.ORR
Yi, COVID-19: what has been learned and to be learned about the novel coronavirus disease, Int J Biol Sci,
doi:10.7150/ijbs.45134
Zahra, The role of folic acid in the management of respiratory disease caused by COVID-19
Zhou, Zhao, Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2, Int J Biol Sci,
doi:10.7150/ijbs.45123