We calculated the interaction binding energies of the drugs capreomycin and streptomycin in complex with the tuberculosis bacterial ribosome subunits.

The current pandemic of coronavirus disease 2019 (COVID‐19), transmitted person‐to‐person by severe acute respiratory syndrome of coronavirus 2 (SARS‐CoV‐2), poses a threat to global public health. To present, these are still no clinically approved antibodies or drugs specific for SARS‐CoV‐2, which makes it difficult for controlling the associated pandemic, limited to monitoring and containment. This situation generates a new need for the development of safe and effective treatments. Since SARS‐CoV‐2 shares phylogenetic traits with SARS‐CoV and MERS‐CoV, antiviral medicines may provide some insight into the development of COVID‐19 therapeutics. Besides that, they are being prioritized several FDA‐approved drugs due to the pandemic state. Despite recent advances in the control of the current COVID‐19 pandemic, challenges such as the rapid virus spread and the socioeconomic cost of this outbreak remain for the inexistence of therapeutics agents against SARS‐CoV‐2. From this moment, the in vivo evaluation of FDA‐approved drugs, which until then appears to be effective are recommended, such as chloroquine, hydroxychloroquine, remdesivir, favipiravir, nitazoxanide, and ivermectin; besides new targets: Mpro, spike glycoprotein, and TMPRSS2 inhibitors. Therefore, these investigations are needed to prove the efficacy and safety of these potential candidates, including their side effects.

The COVID-19 pandemic caused by SARS-CoV-2 continues to pose a major challenge to global health. Targeting the main protease of the virus (Mpro), which is essential for viral replication and transcription, offers a promising approach for therapeutic intervention. In this study, advanced computational techniques such as molecular docking and molecular dynamics simulations were used to screen a series of antiviral compounds for their potential inhibitory effect on the SARS-CoV-2 Mpro. A comprehensive analysis of compounds from the ChemDiv and PubChem databases was performed. The physicochemical properties, pharmacokinetics, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiles were evaluated to determine drug similarity and safety. Compound 4896 − 4038 proved to be the most promising candidate. It exhibited a favorable balance between molecular weight (491.06) and lipophilicity (logP 3.957), high intestinal absorption (92.119%), and broad tissue distribution (VDss of 0.529), indicating good oral bioavailability and therapeutic potential. Molecular docking studies showed that 4896 − 4038 has a strong binding affinity to the active site of Mpro and forms key interactions, such as hydrogen bonds, carbon-hydrogen bonds, pi-sulfur, and multiple van der Waals and pi-pi stacked bonds. The binding energy was comparable to that of the reference drug X77, indicating potential efficacy. Molecular dynamics simulations over 300 ns confirmed the stability of the Mpro/4896 − 4038 complex of protein-ligand. Free energy landscape mapping and MM/PBSA calculations further substantiated the favorable binding and stability of the complex. Importantly, 4896 − 4038 exhibited a comparatively favorable safety profile. In summary, compound 4896 − 4038 shows significant potential as a potent SARS-CoV-2 Mpro inhibitor, combining potent inhibitory activity with favorable pharmacokinetic and safety profiles. These results support the further development of 4896 − 4038 as a promising therapeutic agent in the fight against COVID-19 that warrants experimental validation and clinical investigation.

Structural representation and graphic panel showing the most relevant residues that contribute to the ZIKV NS2B–NS3–ligand complexes.

MRNA vaccines are a new class of vaccine that can induce potent and specific immune responses against various pathogens. However, the design of mRNA vaccines requires the identification and optimization of suitable antigens, which can be challenging and time consuming. Reverse vaccinology is a computational approach that can accelerate the discovery and development of mRNA vaccines by using genomic and proteomic data of the target pathogen. In this article, we review the advances of reverse vaccinology for mRNA vaccine design against SARS-CoV-2, the causative agent of COVID-19. We describe the steps of reverse vaccinology and compare the in silico tools used by different studies to design mRNA vaccines against SARS-CoV-2. We also discuss the challenges and limitations of reverse vaccinology and suggest future directions for its improvement. We conclude that reverse vaccinology is a promising and powerful approach to designing mRNA vaccines against SARS-CoV-2 and other emerging pathogens.

We provide a detailed picture of the interactions between the androgen receptor T877A mutation and three different compounds used in the treatment of prostate cancer.