Aim: The prevailing crisis caused by the COVID-19 pandemic demands the development of effective therapeutic agents that can be implemented with minimal to zero adverse effects. Background: Vitex negundo L. (VNL) is a medicinal plant with reported efficacy against respiratory diseases and some of the COVID-19 symptoms. Funded by the Department of Science and Technology (DOST), the University of the Philippines – Philippine General Hospital (UP-PGH) is currently conducting clinical trials of VNL and other medicinal plants as adjuvant therapeutic agents against mild cases of COVID-19. The basis for the clinical trials is primarily the pharmacological efficacy of the medicinal plants against respiratory disorders and associated COVID-19 symptoms. Objective: This study assessed the in silico potential of VNL components against SARS-CoV-2 main protease (Mpro), an enzyme that plays an important role in COVID-19, the disease caused by the SARS-CoV-2. Objective: This study assessed the in silico potential of VNL components against SARS-CoV-2 main protease (Mpro), an enzyme that plays an important role in COVID-19, the disease caused by the SARS-CoV-2. Method: Phytochemical mining of VNL components from the literature was conducted. A database consisting of 250 known compounds from different parts of VNL was created and screened against SARS-CoV-2 Mpro using the PyRx virtual screening tool. The most promising components were further subjected to in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses using the SwissADME web server and Toxtree software. Results: Virtual screening revealed that 102 VNL components in the database had comparable to or better binding affinities toward SARS-COV-2 Mpro than known chemical inhibitors (e.g. N3 and carmofur). It was determined that the active site of SARS-CoV-2 Mpro receptor consists of multiple H-donor and acceptor sites; hence, the most stable receptor-ligand complexes are generally formed by VNL ligands that establish effective H-bonding with the SARS-CoV-2 Mpro. The promising components, representing a “cocktail” of potential inhibitors also revealed interesting ADMET properties. Conclusion: This in silico study identified VNL as a potential single source of a cocktail of SARS-CoV-2 Mpro inhibitors and a promising adjuvant therapeutic agent against COVID-19 or its symptoms. Furthermore, the study offers a rationale on phytochemical mining from medicinal plants as a means that can be implemented in the early stage of a drug discovery and development program.

Euphorbia hirta L. is a medicinal plant widely used in the Philippines and across tropical Asia against various diseases, including respiratory disorders. In this study, the phytochemical components of E. hirta were investigated in silico for their potential to inhibit the severe acute respiratory syndrome-coronavirus-2 main protease (SARS-CoV-2 Mpro), a coronavirus disease 2019 (COVID-19) drug target that plays a critical role in the infection process of SARS-CoV-2. Phytochemical mining in tandem with virtual screening (PM-VS) was the strategy implemented in this study, which allows efficient preliminary in silico assessment of the COVID-19 therapeutic potential of the reported phytochemicals from the plant. The main rationale for considering E. hirta in the investigation was its reported efficacy against respiratory disorders. It is very promising to investigate the phytochemicals of E. hirta for their potential efficacy against diseases, such as COVID-19, that also target the respiratory system. A total of 298 E. hirta phytochemicals were comprehensively collected from the scientific literature. One hundred seventy of these phytochemicals were computed through molecular docking and were shown to have comparable or better binding properties (promising inhibitors) toward SARS-CoV-2 Mpro than known in vitro inhibitors. In connection to our previous work considering different medicinal plants, antiviral compounds were also rediscovered from the phytochemical composition of E. hirta. This finding provides additional basis for the potential of the plant (or its phytochemicals) as a COVID-19 therapeutic directly targeting drug targets such as SARS-CoV-2 Mpro and/or addressing respiratory-system-related symptoms. The study also highlights the utility of PM-VS, which can be efficiently implemented in the preliminary steps of drug discovery and development.

Monolaurin (ML) is a monoacylglycerol (MAG) with important industrial and biomedical properties. It is commonly prepared in large quantities from the direct esterification of lauric acid (LA) and glycerol with chemical catalysts. However, this method also generates other glyceride by-products whose properties are inferior to ML. Enzymes have also been used to optimize selectivity, but enhancing scalability and throughput is always challenging. Successful selective convergent chemical synthesis of ML involving activated derivatives of LA and glycerol is demonstrated in this study. The present yield of 3.41% can be improved with careful process control.

Blumea balsamifera (L.) DC is a medicinal plant widely used against various ailments throughout Asian and African cultures. The reported efficacy of B. balsamifera and its phytochemicals against respiratory disorders suggests that it can be a potential therapeutic against the coronavirus disease 2019 (COVID-19), which is also a respiratory disease. This potential was demonstrated through an in silico assessment utilizing B. balsamifera phytochemicals and targeting the severe acute respiratory syndrome–coronavirus-2 main protease (SARS-CoV-2 Mpro), an enzyme that plays an important role in the infection process by SARS-CoV-2. The general strategy implemented was termed phytochemical mining in tandem with virtual screening (PM-VS). Data gathering of B. balsamifera phytochemicals reported in the literature was first conducted (PM stage) followed by VS through automated molecular docking of multiple ligands. The present study obtained the most comprehensive phytochemical record and organization of B. balsamifera phytochemicals (a total of 331). Surprisingly, 113 of the unique phytochemicals were promising SARS-CoV-2 Mpro inhibitors, of which 12 were re-discovered antiviral drugs from the plant. The promising inhibitors also reveal interesting in silico drug absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Further analysis of the promising phytochemicals and their interactions with SARS-CoV-2 Mpro hints at the phenylpropanoid moiety (Ph-C3-) as a potential pharmacophore of the target enzyme. This study illustrated the utility of PM-VS in the preliminary stages of drug discovery and development; however, further studies (e.g. exhaustive VS and definitive “ex silico” experiments) are needed to confirm the present finding.