Investigating Multi-Target Antiviral Compounds by Screening of Phytochemicals From Neem (Azadirachta indica) Against PRRSV: A Vetinformatics Approach

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is a global health problem for pigs. PRRSV is highly destructive and responsible for significant losses to the swine industry. Vaccines are available but incapable of providing adequate and long-term protection. As a result, effective and safe strategies are urgently needed to combat the virus. The scavenger receptor cysteine-rich domain 5 (SRCR5) in porcine CD163, non-structural protein 4 (Nsp4), and Nsp10 are known to play significant roles in PRRSV infection and disease development. Therefore, we targeted these proteins to identify multi-target antiviral compounds. To identify potent inhibitors, molecular docking of neem phytochemicals was conducted; three compounds [7-deacetyl-7-oxogedunin (CID:1886), Kulactone (CID:15560423), and Nimocin (CASID:104522-76-1)] were selected based on the lowest binding energy and multi-target inhibitory nature. The efficacy and safety of the selected compounds were revealed through the pharmacokinetics analysis and toxicity assessment. Moreover, 100 ns molecular dynamics (MD) simulation was performed to evaluate the stability and dynamic behavior of target proteins and their docked complexes with selected compounds. Besides, molecular mechanics Poisson–Boltzmann surface area method was used to estimate the binding free energy of each protein-ligand complex obtained from the MD simulations and validate the affinities of selected compounds to target proteins. Based on our analysis, we concluded that the identified multi-target compounds can be utilized as lead compounds for the development of natural drugs against PRRSV. If further validated in clinical studies, these compounds can be used individually or in combination against the virus.

Evaluation of Proanthocyanidins from Kiwi Leaves (Actinidia chinensis) against Caco-2 Cells Oxidative Stress through Nrf2-ARE Signaling Pathway

“…Moreover, real-time PCR, in combination with Western blot and florescent confocal microscopy, could reflect the molecular level of the genotype and phenotype relationship, through antioxidant enzymes gene expression [ 20 ]. Additionally, molecular docking is an effective tool for investigating the best intermolecular framework between bioactive phytochemicals, cellular proteins, and biological macromolecules, in order to clarify the potential mechanisms of their interactions [ 21 , 22 ].…”

“…Moreover, real-time PCR, in combination with Western blot and florescent confocal microscopy, could reflect the molecular level of the genotype and phenotype relationship, through antioxidant enzymes gene expression [20]. Additionally, molecular docking is an effective tool for investigating the best intermolecular framework between bioactive phytochemicals, cellular proteins, and biological macromolecules, in order to clarify the potential mechanisms of their interactions [21,22]. Thus, the aim of this study was to characterize kiwi leaves PAs' viable antioxidant activity against Caco-2 cells, and to emphasize the potential pathways that cause that mode of action through their binding efficiency to the ARE from their impacts on NRF2-Keap1 complexes.…”

Vetinformatics from functional genomics to drug discovery: Insights into decoding complex molecular mechanisms of livestock systems in veterinary science

“…Currently, veterinarians face many challenges exacerbated by climate change, including the emergence of new diseases, as well as those of a rapidly growing human population that requires adequate food and nutrition. Therefore, integration of interdisciplinary approaches with veterinary science is urgently needed to decode the complex molecular mechanisms of livestock systems (5)(6)(7).…”

“…In recent years, the veterinary science community has sought to use these approaches in their research. Therefore, the concept of vetinformatics has been introduced as a branch of bioinformatics that focuses on livestock animals for quality veterinary services (5,30).…”

“…In veterinary science, the livestock production system is a complex process that has three interconnected basic components: animal biology, the environment, and management techniques (31). Therefore, vetinformatics approaches are required to bridge the gaps between genotype and phenotype in order to improve livestock productivity and sustainability (5,30). Large animal datasets have been produced as a result of improvements in various omics platforms and next-generation sequencing (NGS) technologies.…”