The black tiger shrimp (Penaeus monodon) presents a highly nutritious choice for human consumption, renowned for its substantial protein content and abundant supply of vitamins, minerals, unsaturated fatty acids, vital amino acids, and antioxidants. Consequently, the shrimp industry has expanded uninterruptedly, firmly establishing its economic importance in the Blue Revolution. The global commercial production of black tiger shrimp amounted to 4200 million metric tons (mt) in the most recent fiscal year, with an estimated worth of USD 4.8 billion. The high demand in local and international markets has led to the prominence of black tiger prawn farming across the coastal regions of Asia, Australia, and numerous Pacific Island countries. Bangladesh, contributing 2.5% to global shrimp production, generated around USD 300 million as the second largest source of export earnings in the previous economic year by exporting 29,000 mt of black tiger shrimp. In addition, around 1.2 million individuals depend on the P. monodon sector for their source of income in Bangladesh. However, the catastrophic effects of various viral diseases have negatively impacted the shrimp industry. The extremely pathogenic White Spot Syndrome Virus (WSSV), which causes White Spot Disease (WSD), has been a major concern for over thirty years. It infects P. monodon at various stages of development, and causes severe disease outbreaks, leading to a mortality rate of up to 100% within 3–10 days. WSD manifests through a range of clinical symptoms, including lethargy, decreased food intake, reduced cleaning behavior, cuticle detachment, and hepatopancreas discoloration. It is a destructive viral infection that can result in the total loss of shrimp production, imposing a significant economic strain on farmers and the entire shrimp industry. Since 1992, the cumulative worldwide economic loss has been estimated to be USD 21 billion, with an annual financial loss approaching USD 1 billion, representing 10% of global production. Unfortunately, there is no known anti-WSSV cure or therapy for shrimp, and limited progress and scientific research have led to its proliferation. In this circumstance, it is inevitable to develop novel treatments to combat the WSSV infection of shrimp.
Naim Uddin Forhad
To identify the effective strategy for infection of WSSV, research has been conducted on the entry process, specifically the virus’s attachment and recognition to the surface of its host cell. Since entry into the host cell is the first step of viral infection, propagation, and persistence, inhibition of this process by designing anti-viral drugs targeting the envelope proteins is expected to be an effective antiviral strategy. WSSV is a rod-shaped, enveloped, double-stranded DNA virus that contains 184 open reading frames (ORFs) with 22 envelope proteins, including VP28, VP24, VP19, VP26, and VP28, the most abundant and major surface protein, is among the first molecules to interact with host cell receptors. Moreover, it forms a complex by interacting with VP26 and VP24 and is involved in systemic infection. VP28 plays a significant role in the “infectome” which is essential for cell recognition, facilitating the attachment and navigation of the virus into the shrimp cell. The VP28 protein has a nine-stranded β-barrel structure and a protruding N-terminal region. This feature allows it to interact with the host receptor PmRab7, a membrane-associated GTP-binding receptor located in the endosome. Additionally, it facilitates fusion with the host cell membrane to make viral particle transfer more efficient. It has been observed that VP28 naturally assembles into a trimer within the viral envelope, potentially influencing the infective mode of the virus. Therefore, the VP28 trimer is the optimal target for antiWSSV drugs. Blocking its interaction in the endocytic pathway could significantly combat the infection.
Naim Uddin Forhad
Several medicinal plants have been discovered to have bioactive compounds that possess antiviral drug properties. Plant-based drugs are widely accessible, cheaper, safe, and effective with very few side effects. Hence, the rational approach would be identifying and developing effective treatments for viral infections in aquaculture by discovering new plant-based compounds and small molecules that selectively interact with viral proteins. The processes involved in the introduction of new efficient drugs often require significant time, financial resources, and extensive labor. In contrast, the computational methods could potentially reduce the expenses and time in developing a drug candidate. Computer-aided drug design (CADD) exemplifies a sophisticated method for effectively exploring pharmacological libraries to discover potential new therapeutics. The in-silico virtual screening (VS) method enables the rapid and economical identification of drug treatments by generating hits for lead compounds more efficiently. As a result, progress in computational drug design has significantly reduced the time required to conceptualize, develop, and refine a drug. Moreover, employing CADD has facilitated the identification, validation, and exploration of diverse biological and physiological properties of plant bioactive constituents. Figuring out the binding mechanisms may offer significant insights for the development of new anti-WSSV drugs. In earlier in-silico research, it was discovered that withanolide, coagulin Q, and withanolide D from Withania somnifera could help fight the WSSV by targeting the VP26 protein and stopping the formation of mature virion. In another in-silico study, Dinesh et al. identified potential inhibitors of WSSV envelope proteins such as VP26, VP28, and VP110 from Phyllanthus amarus. Despite numerous in silico studies that have explored the efficacy of several medicinal plant compounds on WSSV envelope proteins, none have evaluated the antiviral efficacy of Azadirachta indica and Bacopa monnieri compounds against WSSV. To address this inquiry, we evaluated the compounds obtained from these two plants to determine their potential as new therapeutic candidates against the WSSV VP28 envelope protein. The extracts of A. indica have numerous beneficial properties, such as antiinflammatory, anti-hyperglycemic, anti-carcinogenic, antioxidant, immune-modulatory, anti-mutagenic, anti-ulcer, and anti-viral effects. Similarly, the methanolic extract of B. monnieri has been shown exhibiting antimicrobial, antifungal, antiviral, and neuroprotective activities, highlighting the extensive historical use of these plants for drug development. This study aims to identify and evaluate bioactive compounds from A. indica and B. monnieri as potential inhibitors of the WSSV VP28 envelope protein. Our objective was to identify potential hit compounds from these plants using a readily available integrated bioinformatics approach. This approach utilized a comprehensive computational methodology encompassing virtual screening, pharmacokinetics and toxicity analysis, molecular dynamics (MD) simulation, and MM-PBSA binding energy estimation. Fig. 1 illustrates the possible mechanism by which these flavonoids interact with VP28, thereby inhibiting the viral entry by binding with the host receptor PmRab7. The findings of this study indicate that these compounds could potentially exhibit antiviral properties against the VP28 envelope protein, which may provide new avenues for antiviral strategies to address WSSV.
Shahin Alam
