Virus-host protein-protein interactions as molecular drug targets for arboviral infections

Abstract

Arboviruses have the potential to spread quickly and cause a global health emergency. These are RNA viruses that use RNA-dependent RNA polymerase (RdRp) for their replication. RdRp lacks proofreading activity, leading to high error rates, low replicative fidelity, and more genetic variability. In addition, shorter generation time and faster evolutionary rate of these viruses lead to re-emergence and recurrence of arboviral infections due to the emergence of new variants and the development of antiviral resistance. During the replication inside the host cell through protein-protein interactions (PPIs), these viruses interact with several host factors and utilize the host cellular machinery for their benefit. Besides this, viruses employ several transmission strategies to combat host innate and adaptive immune responses by manipulating the signaling and metabolic pathways of the hosts. Hence, antiviral therapies targeting host-virus PPIs can provide an alternative broad-spectrum strategy against RNA viruses. The approach of targeting virus-specific proteins for developing antivirals is expected to solve the problem of antiviral drug resistance and combat emerging new variants of these viruses. This review focuses on host-virus PPIs of arboviral infections that directly affect the host immune signaling and metabolic pathways. Better understanding of these mechanisms will develop new therapeutic tools to treat viral infections.

Neurological manifestations of Flaviviridae, Togaviridae, and Peribunyaviridae as vector‐borne viruses

“…These proteins may influence the progression of infection within the nervous system, affecting the severity and nature of neurological manifestations. 76 For instance, nsP2 has been implicated in inhibiting host cell transcription and translation, potentially impacting neural cell function.…”

“…Non‐structural proteins, particularly nsP1, nsP2, nsP3, and nsP4, are involved in viral replication and modulating host cellular processes. These proteins may influence the progression of infection within the nervous system, affecting the severity and nature of neurological manifestations 76 . For instance, nsP2 has been implicated in inhibiting host cell transcription and translation, potentially impacting neural cell function.…”

Prediction of motif-mediated viral mimicry through the integration of host–pathogen interactions

“…Viruses, as obligatory pathogens, depend on host cellular machinery for replication, establishing intricate interactions with host proteins throughout their life cycle. These interactions involve hijacking cellular components and countering host defences, posing challenges in the timely identification of targeted viral and host proteins (Rampersad and Tennant 2018 ; Sumbria et al 2020 ; Bhutkar et al 2022 ). Molecular mimicry by viruses, particularly through Short Linear Motifs (SLiMs) (Glavina et al 2018 ; Venkatakrishnan et al 2020 ; Idrees and Paudel 2023a ; Idrees et al 2023 ), has become an intriguing area of study, allowing viruses to effectively replicate, colonise host cells, and evade detection (Benedict et al 2002 ; Finlay and McFadden 2006 ; Hraber et al 2020 ; Goswami et al 2023 ; Mihalič et al 2023 ).…”

Elucidation of antiviral mechanisms of natural therapeutic molecules Herbacetin and Caffeic acid phenethyl ester against chikungunya and dengue virus

“…Viral genomes lack protein synthesis machinery, and the ability to hijack the host cell's resources for their replication is crucial for all viruses. Viruses use various strategies for replication by controlling the host cell's metabolic activities, including exploiting the host lipid pathway, targeting the host glycolytic pathway, hijacking the host ubiquitination pathways, and using the polyamine metabolic pathway [10], [11]. Hence, targeting host factors responsible for virus propagation can be used to develop broad-spectrum antivirals.…”