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.

Due to the limited availability of antifungal drugs, their relevant side effects and considering the insurgence of drug-resistant strains, novel antifungal agents are urgently needed. To identify such agents, we have developed an integrated computational and biological screening platform. We have considered a promising drug target in antifungal drug discovery (exo-1,3-β-glucanase) and a phytochemical library composed of bioactive natural products was used. These products were computationally screened against the selected target using molecular docking and molecular dynamics techniques along with the evaluation of drug-like profile. We selected sesamin as the most promising phytochemical endowed with a potential antifungal profile and satisfactory drug-like properties. Sesamin was submitted to a preliminary biological evaluation to test its capability to inhibit the growth of several Candida species by calculating the MIC/MFC and conducting synergistic experiments with the marketed drug fluconazole. Following the screening protocol, we identified sesamin as a potential exo-1,3-β-glucanase inhibitor, with relevant potency in inhibiting the growth of Candida species in a dose-dependent manner (MIC and MFC of 16 and 32 µg/mL, respectively). Furthermore, the combination of sesamin with fluconazole highlighted relevant synergistic effects. The described screening protocol revealed the natural product sesamin as a potential novel antifungal agent, showing an interesting predicted pharmacological profile, paving the way to the development of innovative therapeutics against fungal infections. Notably, our screening protocol can be helpful in antifungal drug discovery.

The emergence of highly drug-resistant fungal strains is the major concern in health care sector. There is an urgent need to develop novel and potent antifungal drugs with minimal side effects to encounter invasive fungal infections. In this study, we have green-synthesized silver nanoparticles (AgNPs) by using leaf extract of Selaginella bryopteris and checked their antifungal activity against different Candida spp. The optimization of parameters involved in the synthesis of AgNPs includes pH, temperature, concentration of silver nitrate, reaction time. The synthesis of NPs was investigated by the UV–Vis spectrophotometric analysis. The physicochemical properties of AgNPs were further analysed by FESEM, TEM, DLS, zeta potential, FTIR and XRD studies. AgNPs were found to be spherical in shape with an average size of 35 nm and were monodispersed in nature without any agglomeration. The results of antifungal susceptibility testing (AFST) and growth curve kinetics revealed that AgNPs displayed significant anticandidal activity with MIC and MFC values of 0.003 and 0.006 ng/mL respectively. Treatment of Candida spp. with AgNPs leads to damage in fungal cell wall, cell membrane along with disruption of mitochondrial enzyme activity and release of nuclear content. The green-synthesized AgNPs not only caused damage and destruction to the morphology of Candida but also affected the ergosterol biosynthetic pathway. The green-synthesized AgNPs were also found to exhibit antibiofilm activity against Candida spp. which was assessed by crystal violet assay and SEM analysis confirming biofilm reduction by 80–82% as compared to control.