Curative Potential of High-Value Phytochemicals on COVID-19 Infection.

Medicinal plants and their therapeutically promising chemical compounds belonging to the valued category of 'traditional medicine' are potential remedies for various health problems. Due to their complex structure and enormous health benefits, the high-value plant-derived metabolites collectively termed as 'phytochemicals' have emerged as a crucial source for novel drug discovery and development. Indeed, several medicinal plants from diverse habitats are still in the 'underexplored' category in terms of their bioactive principles and therapeutic potential. COVID-19, infection caused by the SARS-CoV-2, first reported in November 2019, resulted in the alarming number of deaths (6.61 million), was further declared 'pandemic', and spread of the disease has continued till today. Even though the well-established scientific world has successfully implemented vaccines against COVID-19 within the short period of time, the focus on alternative remedies for long-term symptom management and immunity boosting have been increased. At this point, interventions based on traditional medicine, which include medicinal plants, their bioactive metabolites, extracts and formulations, attracted a lot of attention as alternative solutions for COVID-19 management. Here, we reviewed the recent research findings related to the effectiveness of phytochemicals in treatment or prevention of COVID-19. Furthermore, the literature regarding the mechanisms behind the preventive or therapeutic effects of these natural phytochemicals were also discussed. In conclusion, we suggest that the active plant-derived components could be used alone or in combination as an alternative solution for the management of SARS-CoV-2 infection. Moreover, the structure of these natural productomes may lead to the emergence of new prophylactic strategies for SARS-CoV-2-caused infection.

Artificial Neural Network Based Study Predicting GS-441524 As Potential Inhibitor of SARS COV-2 Activator Protein Furin: A Polypharmacology Approach (preprint)

Furin, a pro-protein convertase, plays a significant role of biological scissor in bacterial, viral, and even mammalian substrates which in turn decides the fate of many viral and bacterial infections along with the numerous ailments caused by cancer, diabetes, inflammations, and neurological disorders. In the wake of the current pandemic caused by the virus SARS COV-2, furin has become the center of attraction for researchers. In the present work, we have searched for novel inhibitors against this interesting human target from FDA-approved antivirals. To enhance the selection of new inhibitors we employed Kohonen’s-artificial neural network-based self-organizing maps for ligand based virtual screening. Promising results were obtained which can help in drug repurposing and network pharmacology studies addressing the errors due to promiscuity/polypharmacology. We found 15 existing FDA antivirals having the potential to inhibit furin. Among these, six compounds have targets on other important human proteins (LDLR, FCGR1A, PCK1, TLR7, DNA and PNP) also. These 15 drugs inhibiting furin could be studied in patients having many viral infections including SARS COV-2, which is known to have many interacting motifs like NSPs, ORFs, and spike protein. We also propose two promising candidate FDA drugs GS-441524 and Grazoprevir (MK-5172) to repurpose as inhibitors of furin. The best results were observed with GS-441524.

Unravelling Vitamins as Wonder Molecules for Covid-19 Management via Structure-based Virtual Screening (preprint)

The emergence situation of coronavirus disease 2019 (COVID-19) pandemic has realised the global scientific communities to develop strategies for immediate priorities and long-term approaches for utilization of existing knowledge and resources which can be diverted to pandemic preparedness planning. Lack of proper vaccine candidate and therapeutic management has accelerated the researchers to repurpose the existing drugs with known preclinical and toxicity profiles, which can easily enter Phase 3 or 4 or can be used directly in clinical settings. We focused to justify even exploration of supplements, nutrients and vitamins to dampen the disease burden of the current pandemic may play a crucial role for its management. We have explored structure based virtual screening of 15 vitamins against non-structural (NSP3, NSP5, ORF7a, NSP12, ORF3a), structural (Spike & Hemagglutinin esterase) and host protein furin. The in silico analysis exhibited that vitamin B12, Vitamin B9, Vitamin D3 determined suitable binding while vitamin B15 manifested remarkable H-bond interactions with all targets. Vitamin B12 bestowed the lowest energies with human furin and SARS-COV-2 RNA dependent RNA polymerase. Furin mediated cleavage of the viral spike glycoprotein is directly related to enhanced virulence of SARS-CoV-2. In contrast to these, vitamin B12 showed zero affinity with SARS-CoV-2 spike protein. These upshots intimate that Vitamin B12 could be the wonder molecule to shrink the virulence by hindering the furin mediated entry of spike to host cell. These identified molecules may effectively assist in SARS-CoV-2 therapeutic management to boost the immunity by inhibiting the virus imparting relief in lung inflammation.