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The SARS‐CoV‐2 3C‐like protease (3CLpro) has emerged as a key target for drug development owing to its crucial role in viral replication of SARS‐CoV‐2 virus. In this study, we employed a ligand‐based virtual screening strategy to identify potential small molecules capable of binding to SARS‐CoV‐2 3CLpro. Using GC376 as a reference compound, we conducted a comprehensive search in a chemical database and identified 178 candidate molecules (CPLs) with structural similarity to GC376. Molecular docking analyses revealed that several CPLs exhibited superior binding affinities to SARS‐CoV‐2 3CLpro compared to GC376. Notably, CPL‐390, CPL‐374, and CPL‐306 displayed the highest binding energies, indicating their potential as inhibitors of SARS‐CoV‐2 3CLpro. Detailed analysis of noncovalent interactions and molecular mechanics generalized Born surface area (MMGBSA) calculations further supported the binding affinity of CPLs to SARS‐CoV‐2 3CLpro. Key interactions with catalytic residues and steric hindrance within the binding pocket highlighted potential inhibition mechanisms for CPL‐306, CPL‐374, and CPL‐390. Moreover, pharmacokinetic analysis indicated that CPL‐306, CPL‐374, and CPL‐390 possessed favorable absorption, distribution, metabolism, and excretion (ADME) properties, positioning them as promising candidates for further drug development. In contrast, GC376 exhibited less favorable pharmacological characteristics, emphasizing the need for novel compounds with improved profiles. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) caused by the Mycobacterium tuberculosis (MTB) pathogen is a serious contagious illness that endangers the public's health. However, TB is treatable but due to the result of ineffective and protracted medication, MDR‐MTB and XDR‐MTB were able to develop, making their eradication highly challenging and necessitating potential treatments to be cured. This study aimed to identify the novel inhibitor for the InhA enzyme, a potential target of MTB. Initially, 2721 phytochemicals libraries were screened for ADME/Tox profiling and 49 phytochemicals were filtered out. Moreover, these phytochemicals with reference inhibitor triclosan were docked against InhA (PDB ID: 1BVR)., were showing binding energies ranging from −9.16–−6.3 kcal/mol, whereas triclosan showed −6.90 kcal/mol of binding energy. The docking results reveal that irilone (−9.16 kcal/mol) and aurantio‐obtusin (−8.84 kcal/mol) exhibit promising binding energy and perfectly occupy the binding site of InhA. Furthermore, molecular dynamics simulation (MDS) and MMGBSA studies showed better affinities of selected compounds in terms of stability, compactness, flexibility, and total BFE in complexes with InhA. This study concluded that irilone and aurantio‐obtusin could be promising InhA inhibitors based on their impressive pharmacokinetic profiling, toxicity, binding affinity, and stability. However experimental validation is a subject of further research. [ABSTRACT FROM AUTHOR]

The enzyme Heme O Synthase (HOS) is essential for producing heme A and heme O, which are critical for defense against reactive oxygen species, drug detoxification, gas synthesis, transport, and electron transport in Plasmodium species. It has become vital to discover inhibitory molecules/compounds/medicines that target the synthesis of heme due to the emergence of drug‐resistant strains of Plasmodium falciparum. Therefore, in this study, we employed molecular mechanics with Generalized Born surface area (MMGBSA) calculations and docking studies to investigate potential antimalarial compounds targeting HOS from antimalarial botanicals. Screening these compounds, we have identified 2 compounds; Meliantrol and Tamarixetin with better binding affinities (−8.4 Kcal/mol and −8.3 Kcal/mol respectively) than the current standard inhibitor(Inabenfide) of HOS (−8.0 Kcal/mol). The MMGBSA calculations provided insight into the thermodynamics of the binding process and helped identify key interactions responsible for the stability of the HOS‐ligand complex. In addition, the 2 compounds were further screened comparatively with the standard HOS inhibitor considering their protein‐ligand interaction profile and ADMET profile and these 2 selected compounds outperformed Inabenfide. Our results predict that these compounds are potential drug candidates with domiciled therapeutic functions against Malaria therefore, open doors for more experimental validations for drug development. [ABSTRACT FROM AUTHOR]