An integrated virtual screening of compounds from Carica papaya leaves against multiple protein targets of SARS-Coronavirus-2

Abstract

The pandemic of SARS-Coronavirus-2 (Coronavirus-19) has been progressing by the increasing trend of the cases as well as deaths with neither vaccine nor drug is rationally used to stop the viral spread over. This study aims to perform an integrated virtual screening of compounds that had been identified from Carica papaya leaves, which are proposed to be a herbal treatment for SARS-Coronavirus-2. The screening was initiated by evaluating the 40 compounds from Carica papaya leaves for their drug-like likeness property. The selected compounds were then secondly screened using carcinogenic and toxicity filters. Further selected compounds were thirdly screened for their pharmacokinetic profile and the screening was lastly performed by docking the third selected compounds against multiple protein targets of SARS-Coronavirus-2 employing 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), RNA-dependent-RNA-polymerase (RdRp), endonuclease (EndoU), S1 and S2 region of spike protein. The results show that 20 of 40 compounds, which meet the requirements of drug-like likeness, carcinogenicity-toxicity filter, and pharmacokinetic profiles, can interact with the multiple protein targets of SARS-Coronavirus-2 with the order from high to low affinity as follows: S1 > 3CLpro > EndoU > RdRp > PLpro > S2. In conclusion, Carica papaya leaves are worth to be proposed for further in vitro study against SARS-Coronavirus-2 at both molecular and cellular levels.

Potential SARS-CoV-2 3CLpro inhibitors from chromene, flavonoid and hydroxamic acid compound based on FRET assay, docking and pharmacophore studies

“…The extracts were obtained in the same physical and chemical conditions with the previous study conducted [35] , [36] as it was stored in −20 °C with nitrogen exposure before tightly sealed and its stability was confirmed using thin layer chromatography (TLC). As presented in Fig.…”

“…In this present study, we have performed in vitro testing for those three plants extracts against SARS-CoV-2 3CLpro enzyme. In addition, we also tested papaya ( Carica papaya ) leaves methanolic extract as this plant had been reported to increase the platelet and leukocyte counts in DENV2‐infected AG129 mice associated to the dengue protease inhibition [36] . The most active extract was identified for its existing compounds using gas chromatography-mass spectrometry (GC–MS) and the identified compounds were studied its pharmacophore.…”

2-Phenoxyacetamide derivatives as SARS-CoV-2 main protease inhibitor: In silico studies

“…SARS-CoV-2 is composed by structural proteins (spike, membrane, envelope, capsid, ssRNA) and the non-structural proteins (nsp1-nsp16) with their integrated function to maintain the virus life cycle [7] . Main protease (M pro ) is the nsp5 having a function in the polypeptide1a and polypeptide1ab proteolysis to yield various small protein fragments to further be constructed and packed in new virions [8] . Therefore, by inhibiting this enzyme, the new virion formation would be canceled leading to a stopped viral replication [9] .…”

The Future of Carica papaya Leaf Extract as an Herbal Medicine Product

“…Phytochemical compounds have been identified in papaya leaf, mostly in such classes of flavonoids as apigenin, catechin, deoxyquercetin, hesperitin, isorhamnetin, kaempferol, myricetin, naringenin, protocatechuic acid, quercetin, and rutin. Meanwhile, the fruit is enriched by amino acids, proteins, carbohydrates, fibre, vitamin C, and other nutrients [39]. Interestingly, the all parts of papaya mainly express the white latex, which contains high contents of a proteolytic enzyme called papain, which has been studied in relation to its crucial role in the pathophysiology of many diseases, as well as for drug design, and industrial uses such as in meat tenderizers and pharmaceutical preparations [40].…”