Polo-like kinase-1 (PLK-1) is an essential mitotic serine/threonine (Ser/Thr) kinase that belongs to the Polo-like kinase (PLK) family and is overexpressed in non-small cell lung cancer (NSCLC) via promotion of cell division. Therefore, PLK-1 may act as a promising target for the therapeutic cure of various cancers. Although a variety of anti-cancer drugs, both synthetic and naturally occurring, such as volasertib, onvansertib, thymoquinone, and quercetin, are available either alone or in combination with other therapies, they have limited efficacy, especially in the advanced stages of cancer. To the best of our knowledge, no anticancer agent has been reported from marine algae or microorganisms to date. Thus, the aim of the present study is a high-throughput virtual screening of phlorotannins, obtained from edible brown algae, using molecular docking and molecular dynamic simulation analysis. Among these, Pentafuhalol-B (PtB) showed the lowest binding energy (best of triplicate runs) against the target protein PLK-1 as compared to the reference drug volasertib. Further, in MD simulation (best of triplicate runs), the PtB-PLK-1 complex displayed stability in an implicit water system through the formation of strong molecular interactions. Additionally, MMGBSA calculation (best of triplicate runs) was also performed to validate the PtB-PLK-1 complex binding affinities and stability. Moreover, the chemical reactivity of PtB towards the PLK-1 target was also optimised using density functional theory (DFT) calculations, which exhibited a lower HOMO-LUMO energy gap. Overall, these studies suggest that PtB binds strongly within the pocket sites of PLK-1 through the formation of a stable complex, and also shows higher chemical reactivity than the reference drug volasertib. The present study demonstrated the inhibitory nature of PtB against the PLK-1 protein, establishing its potential usefulness as a small molecule inhibitor for the treatment of different types of cancer.

The present study explores the efficacy of plant-derived natural products (PDNPs) against spike glycoproteins (S-glycoprotein) of SARS-CoV-2 variants using molecular docking, ADMET, molecular dynamics (MD) simulation and density-functional theory (DFT) analysis. In all, 100 PDNPs were screened against spike glycoprotein of SARS-CoV-2 variants, namely alpha (B.1.1.17), beta (B.1.351), delta (B.1.617), gamma (P.1) and omicron (B.1.1.529). Results showed that rutin, EGCG, hesperidin, withanolide G, rosmarinic acid, diosmetin, myricetin, epicatechin and quercetin were the top hit compounds against each of the SARS-CoV-2 variants. The most active compounds, rutin, hesperidin, EGCG and rosmarinic acid gave binding scores of −10.2, −8.1, −8.9, −8.3 and −9.2 kcal/mol, against omicron, delta, alpha, beta and gamma variants, respectively. Further, the stability of docked complexes was confirmed by the analysis of molecular descriptors (RMSD, RMSF, SASA, Rg and H-bonds) in molecular dynamic simulation analysis. Moreover, the physiochemical properties and drug-likeness of the tested compounds showed that they have no toxicity or carcinogenicity and may be used as druggable targets. In addition, the DFT study revealed the higher activity of the tested compounds against the target proteins. This led us to conclude that rutin, hesperidin, EGCG and rosmarinic acid are good candidates to target the S-glycoproteins of SARS-CoV-2 variants. Further, in vivo and clinical studies needed to develop them as drug leads against existing or new SARS-CoV-2 variants are currently underway in our laboratory.

Recently, a new and fatal strain of coronavirus named as SARS-CoV-2 (Disease: COVID-19) appeared in Wuhan, China in December of 2019. Due to its fast growing human to human transmission and confirmed cases in nearly every country, it has been declared as pandemic by World Health Organisation (WHO) on 11 March 2020. Till now, there is no therapy such as vaccines and specific therapeutic agents available globally. Inspite of this, some protease inhibitors and antiviral agents namely lopinavir, ritonavir, remdisivir and chloroquine are under investigation and also implemented in several countries as therapeutic agents for the treatment of COVID-19. Seeing the health crisis across the world, it was our aim to find out a suitable drug candidate which could target SARS-CoV-2. For this purpose, molecular docking of 7 proteinsof SARS-CoV-2 was done with 18active constituents that have previously been reported to be antiviral or anti-SARS-CoV agents. The docking results of these 18 compounds were compared with 2 FDA approved drugs that have are currently being used in COVID 19, namely Remdesivir and Chloroquine. Our result revealed that among all, epigallocatechin gallate (EGCG), a major constituent of green tea, is the lead compound that could fit well into the binding sites of docked proteins of SARS-CoV-2. EGCG showed very strong molecular interactions with binding energies -9.30, -8.66, -8.38, -7.57, -7.26, -6.99 and -4.90 kcal/mole for6y2e, 6vw1, 6vww, 6lxt,6vsb, 6lu7 and 6lvnproteins of SARS-CoV-2, respectively.Therefore, EGCG as per our results, should be explored as a drug candidate for the treatment of COVID-19.

Background: Coronavirus disease-2019 (COVID-19) has recently emerged as a pandemic respiratory disease with mild to severe pneumonia symptoms. No clinical antiviral agent is available so far. However, several repurposing drugs and vaccines are being given to individuals or in clinical trials against SARS-CoV-2 Objective: The aim of this study is to uncover the potential effects of Luteolin (Lut) as an inhibitor of SARS-CoV2 encoded proteins via utilizing computational tools. Method: Molecular modelling to unfold the anti-SARS-CoV2 potential of Lut along with reference drugs namely remdesivir and nafamostat was performed by the use of molecular docking, molecular dynamic (MD) simulation, absorption, distribution, metabolism, excretion, toxicity (ADMET) and density functional theory (DFT) methods against the five different SARS-CoV-2 encoded key proteins and one human receptor protein. The chemical reactivity of Luteolin is done through prediction of HOMO-LUMO gap energy and other chemical descriptors analysis. Results: In the present study, Lut binds effectively in the binding pockets of spike glycoprotein (6VSB), ADP phosphatase of NSP3 (6W02), and RNA dependent RNA polymerase (7AAP) protein receptors with significant values of docking scores -7.00, -7.25, and -6.46 respectively as compared to reference drugs remdesivir and nafamostat. Conclusion:: Thus, Lut can act as a therapeutic agent and is orally safe for human consumption as predicted by molecular modelling against SARS-CoV-2 in the treatment of COVID-19.