The current research used a virtual screening method to study 57 isolated phytochemicals (alkaloids, phytosterols, and flavonoids) against the SARS-CoV-2 main protease (M^pro). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the selected compounds were analysed using admetSAR tool while SwissADME and Molinspiration chemoinformatics tools were used to examine the oral bioavailability and drug-likeness properties. Parameters such as physicochemical properties, activity spectra for substances (PASS) prediction, bioactivity, binding mode, and molecular interactions were also analysed. Our results favoured Lupeol (–8.6 kcal/mol), Lupenone (–7.7 kcal/mol), Hesperetin (–7.4 kcal/mol), Apigenin (–7.3 kcal/mol) and Castasterone (–7.3 kcal/mol) as probable inhibitors of SARS-CoV-2. This is because of their good binding affinities, bioactivities, drug-likeness, ADMET properties, PASS properties, oral bioavailability, binding mode and their interactions with the active site of the target receptor compared to Remdesivir and Azithromycin. Therefore, these compounds could be explored towards the development of new therapeutic agents against SARS-CoV-2. Graphical Abstract

Fungal infection has become a persistent problem in humans and is sometimes life-threatening in immune-compromised individuals. This work aims to study phytochemicals from Annona muricata (sour sop) as probable antifungal agents against Candida albicans sterol 14α-demethylase target receptor by Computer Aided-Drug Design (CADD) approach using voriconazole and fluconazole as standard drugs. A modern method of drug discovery by molecular docking and chemoinformatics was used to screen 131 isolated phytochemicals with medicinal properties from Annona muricata against Candida albicans ‘sterol 14α-demethylase, a prominent target receptor for most anti-fungal drugs, towards the development of new anti-fungal therapeutic agents and a new approach to treat patients with fungal infections. The compounds were all subjected to analyses like ADMET, drug-likeness, bioactivity, oral-bioavailability and PASS. The results of the docking simulation and chemoinformatics analyses showed that muricin M (-7.9 kcal/mol), chlorogenic acid (-8.2 kcal/mol), roseoside (-8.5 kcal/mol) and caffeoylquinic acid (-8.1 kcal/mol) are potential drug candidates for treating fungal infections due to their excellent properties such as binding affinities, ADMET profile, drug-likeness, bioactivity, binding mode and interactions with the target receptor. Thus, muricin M, chlorogenic acid, roseoside and caffeoylquinic acid are recommended for further analyses towards the development of further antifungal drugs.

The rising incidence of Mpox cases calls for urgent and concerted efforts to identify effective therapeutics in the treatment of the disease. This research article explores standard antimicrobial agents as potential inhibitors of Mpox through in silico analysis targeting the 8CEQ protein, which is key in the survival of the virus. A comprehensive molecular docking approach was employed to assess the binding affinities of 21 common antimicrobial agents used in the treatment of various bacterial infections. This was subsequently followed by ADMET profiling, oral bioavailability analysis, and bioactivity assessments. Twelve (12) ligands were screened for critical properties influencing drug-likeness, including molecular weight, polar surface area, lipophilicity, flexibility, and solubility. Ceftriaxone had the highest binding affinity at-8.1 kcal/mol, followed by Cefepime (-7.5 kcal/mol). The Molecular Dynamics Simulation (MDS) results of the Ceftriaxone_8ceq and Cefepime_8ceq complexes validate their stable interactions in the active site of the Mpox drug target, although Cefepime_8ceq complex was more stable than the Ceftriaxone_8ceq complex. Overall, our findings suggest that Cefepime, Ceftriaxone, Nitrofurantoin, Trimethoprim, Gentamycin, and Cefotetan demonstrate promising inhibitory potentials against Mpox. These results underscore the utility of in silico methodologies in rapid drug repurposing efforts for emerging viral infections. While noting that most of the antimicrobial agents involved in the study were used not only orally but also through other routes of administration, the spectrum of findings suggests that though they have potential for the inhibition of the viral infection, further optimization and development of the identified ligands is required towards the development of reliable and safer novel anti-Mpox therapeutic agents.