Screening and Druggability Analysis of Marine Active Metabolites against SARS-CoV-2: An Integrative Computational Approach

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered a recent pandemic of respiratory disease and affected almost every country all over the world. A large amount of natural bioactive compounds are under clinical investigation for various diseases. In particular, marine natural compounds are gaining more attention in the new drug development process. The present study aimed to identify potential marine-derived inhibitors against the target proteins of COVID-19 using a computational approach. Currently, 16 marine clinical-level compounds were selected for computational screening against the 4 SARS-CoV-2 main proteases. Computational screening resulted from the best drug candidates for each target based on the binding affinity scores and amino acid interactions. Among these, five marine-derived compounds, namely, chrysophaentin A (-6.6 kcal/mol), geodisterol sulfates (-6.6 kcal/mol), hymenidin (-6.4 kcal/mol), plinabulin (-6.4 kcal/mol), and tetrodotoxin (-6.3 kcal/mol) expressed minimized binding energy and molecular interactions, such as covalent and hydrophobic interactions, with the SARS CoV-2 main protease. Using molecular dynamic studies, the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (ROG), and hydrogen bond (H-Bond) values were calculated for the SARS-CoV-2 main protease with a hymenidin docked complex. Additionally, in silico drug-likeness and pharmacokinetic property assessments of the compounds demonstrated favorable druggability. These results suggest that marine natural compounds are capable of fighting SARS-CoV-2. Further in vitro and in vivo studies need to be carried out to confirm their inhibitory potential.

Plant in vitro Culture Technologies; A Promise Into Factories of Secondary Metabolites Against COVID-19.

The current pandemic has caused chaos throughout the world. While there are few vaccines available now, there is the need for better treatment alternatives in line with preventive measures against COVID-19. Along with synthetic chemical compounds, phytochemicals cannot be overlooked as candidates for drugs against severe respiratory coronavirus 2 (SARS-CoV-2). The important role of secondary metabolites or phytochemical compounds against coronaviruses has been confirmed by studies that reported the anti-coronavirus role of glycyrrhizin from the roots of Glycyrrhiza glabra. The study demonstrated that glycyrrhizin is a very promising phytochemical against SARS-CoV, which caused an outbreak in 2002-2003. Similarly, many phytochemical compounds (apigenin, betulonic acid, reserpine, emodin, etc.) were isolated from different plants such as Isatis indigotica, Lindera aggregate, and Artemisia annua and were employed against SARS-CoV. However, owing to the geographical and seasonal variation, the quality of standard medicinal compounds isolated from plants varies. Furthermore, many of the important medicinal plants are either threatened or on the verge of endangerment because of overharvesting for medicinal purposes. Therefore, plant biotechnology provides a better alternative in the form of in vitro culture technology, including plant cell cultures, adventitious roots cultures, and organ and tissue cultures. In vitro cultures can serve as factories of secondary metabolites/phytochemicals that can be produced in bulk and of uniform quality in the fight against COVID-19, once tested. Similarly, environmental and molecular manipulation of these in vitro cultures could provide engineered drug candidates for testing against COVID-19. The in vitro culture-based phytochemicals have an additional benefit of consistency in terms of yield as well as quality. Nonetheless, as the traditional plant-based compounds might prove toxic in some cases, engineered production of promising phytochemicals can bypass this barrier. Our article focuses on reviewing the potential of the different in vitro plant cultures to produce medicinally important secondary metabolites that could ultimately be helpful in the fight against COVID-19.

Therapeutic potential of medicinal plants against COVID-19: The role of antiviral medicinal metabolites.

There are numerous trials underway to find treatment for the COVID-19 through testing vaccines as well as existing drugs. Apart from the many synthetic chemical compounds, plant-based compounds could provide an array of \suitable candidates for testing against the virus. Studies have confirmed the role of many plants against respiratory viruses when employed either as crude extracts or their active ingredients in pure form. The purpose of this review article is to highlight the importance of phytomedicine against COVID-19. The main aim is to review the mechanistic aspects of most important phytochemical compounds that have showed potential against coronaviruses. Glycyrrhizin from the roots of Glycyrrhiza glabra has shown promising potential against the previously epidemic coronavirus, SARS-CoV. Other important plants such as Artemisia annua, Isatis indigotica, Lindera aggregate, Pelargonium sidoides, and Glychirrhiza spp. have been employed against SARS-CoV. Active ingredients (e.g. emodin, reserpine, aescin, myricetin, scutellarin, apigenin, luteolin, and betulonic acid) have shown promising results against the coronaviruses. Phytochemicals have demonstrated activity against the coronaviruses through mechanisms such as viral entry inhibition, inhibition of replication enzymes and virus release blockage. However, compared to synthetic drugs, phytomedicine are mechanistically less understood and should be properly evaluated before application. Nonetheless, phytochemicals reduce the tedious job of drug discovery and provide a less time-consuming alternative for drug testing. Therefore, along with other drugs currently tested against COVID-19, plant-based drugs should be included for speedy development of COVID-19 treatment.

Impact of the COVID-19 pandemic on maternal health services in Pakistan.

Throughout the world as health systems are being prepared to deal with the SARS-CoV-2 outbreak which will affect the management of HIV, diabetes, mental health and mainly maternal healthcare systems. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID-19 outbreak, there has been very little concern expressed over the effects on maternal health services. It is highly likely that the present situation may exacerbate maternal mortality in suburban and rural areas. The present situation requires governments and NGOs to make necessary arrangements to support people with prenatal and postnatal care.

The coronavirus (COVID-19) pandemic's impact on mental health.

Throughout the world, the public is being informed about the physical effects of SARS-CoV-2 infection and steps to take to prevent exposure to the coronavirus and manage symptoms of COVID-19 if they appear. However, the effects of this pandemic on one's mental health have not been studied at length and are still not known. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID-19 outbreak, there has been very little concern expressed over the effects on one's mental health and on strategies to prevent stigmatization. People's behavior may greatly affect the pandemic's dynamic by altering the severity, transmission, disease flow, and repercussions. The present situation requires raising awareness in public, which can be helpful to deal with this calamity. This perspective article provides a detailed overview of the effects of the COVID-19 outbreak on the mental health of people.