Butein as a potential binder of human ACE2 receptor for interfering with SARS-CoV-2 entry: a computer-aided analysis.

Natural products have been included in our dietary supplements and have been shown to have numerous therapeutic properties. With the looming danger of many zoonotic agents and novel emerging pathogens mainly of viral origin, many researchers are launching various clinical trials, testing these compounds for their antiviral activity. The present work deals with some of the available natural compounds from the literature that have demonstrated activity in counteracting pathogen infections. Accordingly, we screened, using in silico methods, this subset of natural compounds for searching potential drug candidates able to interfere in the recognition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and its target human angiotensin-converting enzyme 2 (hACE2) receptor, leading to the viral entry. Disrupting that recognition is crucial for slowing down the entrance of viral particles into host cells. The selected group of natural products was examined, and their interaction profiles against the host cell target protein ACE2 were studied at the atomic level. Based on different computer-based procedures including molecular docking, physicochemical property evaluation, and molecular dynamics, butein was identified as a potential hit molecule able to bind the hACE2 receptor. The results indicate that herbal compounds can be effective for providing possible therapeutics for treating and managing coronavirus disease 2019 (COVID-19) infection.

Recent Advances Made in the Synthesis of Small Drug Molecules for Clinical Applications: An Insight

Over decades dependency of humans on the drugs has become indispensable and irreplaceable. Thus, each year many new drugs are licensed. Nonetheless, drugs undergo rigorous testing and analysis to be available globally in economic price for the suitability of patients with different age and physiological conditions. The testing of drugs include phase I clinical trial using small group of 20-100 healthy volunteers for safety, pharmacology and efficacy;phase II clinical trial using 100-500 volunteer patients to optimize effective dose, dose interval, safety analysis and mode of delivery such as oral or intravenous;phase III clinical trial using 1000-5000 in a larger population of patients globally at different international places to collect sufficient safety and efficacy data for patenting and licencing. Moreover, thousands of drugs fail to achieve these objectives. Therefore, this mini-review intends to critically examine and assimilate the clinical applications of selected complex repurposed small drug molecules which are in different phase of trials for treating viral infection including complications due to COVID-19: (a) Remdesivir, (b) Galidesivir, (c) Favipiravir, (d) Baricitinib, and (e) Baloxavir.

Plausible mechanisms explaining the role of cucurbitacins as potential therapeutic drugs against coronavirus 2019.

In the year 2019, the potent zoonotic virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began to rage globally, which resulted in the World Health Organization (WHO) declaring it as a pandemic on March 11th, 2020. Although extensive research is currently ongoing worldwide to understand the molecular mechanism and disease pathogenicity of SARS-CoV-2, there are still many nuances to elucidate. Therefore, developing an appropriate vaccine or therapeutic drug to combat coronavirus 2019 (COVID-19) is exceedingly challenging. Such scenarios require multifaceted approaches to identify suitable contenders for drugs against COVID-19. In this context, investigating natural compounds found in food, spices, and beverages can lead to the discovery of lead molecules that could be repurposed to treat COVID-19. Sixteen cucurbitacin analogues were investigated for activity against the SARS-CoV-2 main protease protein (Mpro), angiotensin-converting enzyme 2 (ACE2) binding receptor, nonstructural protein 12 (NSP12) RNA-dependent RNA polymerase (RdRp), NSP13 helicase, and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway using several relevant tools and simulated screening methods. All key proteins were found to bind efficiently only with cucurbitacin G 2-glucoside and cucurbitacin H with the lowest global energy. Further, the absorption, distribution, metabolism, and excretion (ADME) of all the cucurbitacins were analysed to explore their drug profiles. Cucurbitacin G 2-glucoside and H showed the best hits and all the analogues showed no adverse properties that would diminish their drug-likeness abilities. The encouraging results of the current study may lay the foundation for future research and development of effective measures and preventive medications against SARS-CoV-2.