Antiviral Drug Candidates Research Articles

Identification of a Direct-Acting Antiviral Agent Targeting RNA Helicase via a Graphene Oxide Nanobiosensor.

Dengue virus (DENV), an arbovirus transmitted by mosquitoes, causes infectious diseases such as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Despite the dangers posed by DENV, there are no approved antiviral drugs for treatment of DENV infection. Considering the potential for a global dengue outbreak, rapid development of antiviral agents against DENV infections is crucial as a preemptive measure; thus, the selection of apparent drug targets, such as the viral enzymes involved in the viral life cycle, is recommended. Helicase, a potential drug target in DENV, is a crucial viral enzyme that unwinds double-stranded viral RNA, releasing single-stranded RNA genomes during viral replication. Therefore, an inhibitor of helicase activity could serve as a direct-acting antiviral agent. Here, we introduce an RNA helicase assay based on graphene oxide, which enables fluorescence-based analysis of RNA substrate-specific helicase enzyme activity. This assay demonstrated high reliability and ability for high-throughput screening, identifying a new helicase inhibitor candidate, micafungin (MCFG), from an FDA-approved drug library. As a direct-acting antiviral agent targeting RNA helicase, MCFG inhibits DENV proliferation in cells and an animal model. Notably, in vivo, MCFG treatment reduced viremia, inflammatory cytokine levels, and viral loads in several tissues and improved survival rates by up to 40% in a lethal mouse model. Therefore, we suggest MCFG as a potential direct-acting antiviral drug candidate.

Enabling rapid COVID-19 small molecule drug design through scalable deep learning of generative models

We improved the quality and reduced the time to produce machine learned models for use in small molecule antiviral design. Our globally asynchronous multi-level parallel training approach strong scales to all of Sierra with up to 97.7% efficiency. We trained a novel, character-based Wasserstein autoencoder that produces a higher quality model trained on 1.613 billion compounds in 23 minutes while the previous state of the art takes a day on 1 million compounds. Reducing training time from a day to minutes shifts the model creation bottleneck from computer job turnaround time to human innovation time. Our implementation achieves 318 PFLOPs for 17.1% of half-precision peak. We will incorporate this model into our molecular design loop enabling the generation of more diverse compounds; searching for novel, candidate antiviral drugs improves and reduces the time to synthesize compounds to be tested in the lab.

Compounds Identified from Marine Mangrove Plant (Avicennia alba) as Potential Antiviral Drug Candidates Against WDSV, an In-Silico Approach.

Walleye dermal sarcoma virus (WDSV) is a type of retrovirus, which affects most of the adult walleye fishes during the spawning time. The virus causes multiple epithelial tumors on the fish’s skin and fins that are liable for more than 50% of the mortality rate of fish around the world. Till now, no effective antiviral drug or vaccine candidates have been developed that can block the progression of the disease caused by the pathogen. It was found that the 582-amino-acid (aa) residues long internal structural gag polyprotein of the virus plays an important role in virus budding and virion maturation outside of the cell. Inhibition of the protein can block the budding and virion maturation process and can be developed as an antiviral drug candidate against the virus. Therefore, the study aimed to identify potential natural antiviral drug candidates from the tropical mangrove marine plant Avicennia alba, which will be able to block the budding and virion maturation process by inhibiting the activity of the gag protein of the virus. Initially, a homology modeling approach was applied to identify the 3D structure, followed by refinement and validation of the protein. The refined protein structures were then utilized for molecular docking simulation. Eleven phytochemical compounds have been isolated from the marine plant and docked against the virus gag polyprotein. Three compounds, namely Friedlein (CID244297), Phytosterols (CID12303662), and 1-Triacontanol (CID68972) have been selected based on their docking score −8.5 kcal/mol, −8.0 kcal/mol and −7.9 kcal/mol, respectively, and were evaluated through ADME (Absorption, Distribution, Metabolism and Excretion), and toxicity properties. Finally, molecular dynamics (MD) simulation was applied to confirm the binding stability of the protein-ligands complex structure. The ADME and toxicity analysis reveal the efficacy and non-toxic properties of the compounds, where MD simulation confirmed the binding stability of the selected three compounds with the targeted protein. This computational study revealed the virtuous value of the selected three compounds against the targeted gag polyprotein and will be effective and promising antiviral candidates against the pathogen in a significant and worthwhile manner. Although in vitro and in vivo study is required for further evaluation of the compounds against the targeted protein.

SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (~45.1 nm/s) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.

SMMPPI: a machine learning-based approach for prediction of modulators of protein-protein interactions and its application for identification of novel inhibitors for RBD:hACE2 interactions in SARS-CoV-2.

Small molecule modulators of protein–protein interactions (PPIs) are being pursued as novel anticancer, antiviral and antimicrobial drug candidates. We have utilized a large data set of experimentally validated PPI modulators and developed machine learning classifiers for prediction of new small molecule modulators of PPI. Our analysis reveals that using random forest (RF) classifier, general PPI Modulators independent of PPI family can be predicted with ROC-AUC higher than 0.9, when training and test sets are generated by random split. The performance of the classifier on data sets very different from those used in training has also been estimated by using different state of the art protocols for removing various types of bias in division of data into training and test sets. The family-specific PPIM predictors developed in this work for 11 clinically important PPI families also have prediction accuracies of above 90% in majority of the cases. All these ML-based predictors have been implemented in a freely available software named SMMPPI for prediction of small molecule modulators for clinically relevant PPIs like RBD:hACE2, Bromodomain_Histone, BCL2-Like_BAX/BAK, LEDGF_IN, LFA_ICAM, MDM2-Like_P53, RAS_SOS1, XIAP_Smac, WDR5_MLL1, KEAP1_NRF2 and CD4_gp120. We have identified novel chemical scaffolds as inhibitors for RBD_hACE PPI involved in host cell entry of SARS-CoV-2. Docking studies for some of the compounds reveal that they can inhibit RBD_hACE2 interaction by high affinity binding to interaction hotspots on RBD. Some of these new scaffolds have also been found in SARS-CoV-2 viral growth inhibitors reported recently; however, it is not known if these molecules inhibit the entry phase.

Rational design of flavonoid based potential inhibitors targeting SARS-CoV 3CL protease for the treatment of COVID-19

The current outbreak of Coronavirus Disease 2019 (COVID-19) pandemic has reported thousands of deaths worldwide due to the rapid transmission rate and the lack of antiviral drugs and vaccinations. There is an urgent need to develop potential antiviral drug candidates for the prevention of COVID-19 infection. In the present study, a series of potential inhibitors targeting SARS-CoV 3CL protease were rationally designed by incorporating gamma lactam ring, and various fluoro substituted heterocyclic ring systems to the flavonoid scaffold. The prediction of drug-likeness, oral bioavailability, toxicity, synthetic accessibility, and ADMET properties was made by computational means. Quercetin was used as standard. The binding affinity of the ligands towards the 3CL protease target was examined using docking simulations. The designed ligands possess favourable pharmacokinetic and pharmacodynamic properties. Ligand L4, L8, and L14 appeared to be the lead compounds in the series and can be considered for further in-vivo and in-vitro validation.

Characterization, Antimicrobial and Antioxidant Evaluation of Biofabricated Silver Nanoparticles from Endophytic Pantoea anthophila.

Endophyte mediated nanoparticles fabrication were emerging as a new frontier in nanomedicines that produce high biocompatible and functionalized silver nanoparticles. In this study, silver nanoparticles were successfully biosynthesized from the extracellular extract of endophytic bacterium Pantoea anthophila isolated from the stem of Waltheria indica for the first time. The synthesized nanoparticles showed a strong absorption band at 410 nm in the UV–Visible range. The dynamic light scattering and zeta potential analysis indicated that the average particle size was 16 nm at 5.30 mV. FTIR spectrum displayed the presence of various functional groups at 3423.65, 1633.71, 1022.27, 607.58 cm−1 that stabilised the nanoparticle. X-ray diffraction peaks were conferred to 100, 200, 220 and 311 planes of a face centred cubic structure. TEM and SEM micrograph revealed the spherical-shaped, polycrystalline nature with the presence of elemental silver analysed by EDAX. Selected area electron diffraction also confirms the orientation of silver nanoparticles with X-ray diffraction analysis. Antimicrobial activity against 10 different human pathogenic bacteria and fungi showed a broad spectrum inhibition against both Gram-positive and Gram-negative bacteria. Among the bacterial pathogens, B. Subtilis exhibited low activity compared to other pathogens. C. albicans was greatly controlled than other fungal species. A strong free radical scavenging activity of silver nanoparticles with IC50 values 31.29 ± 0.73, 19.83 ± 1.57, 35.64 ± 0.94, 42.07 ± 1.30, 29.70 ± 2.26, 29.10 ± 0.82, 36.80 ± 0.63 μg/ml was obtained in different antioxidant assays that were comparable to the reference. The study suggests that the silver nanoparticles can be biosynthesized from endophytic P. anthophila metabolites with significant therapeutic potential. With proper validation, the biosynthesized silver nanoparticles can be developed as a promising antiviral and anticancer drug candidate.

A systems-based method to repurpose marketed therapeutics for antiviral use: a SARS-CoV-2 case study.

This study describes two complementary methods that use network-based and sequence similarity tools to identify drug repurposing opportunities predicted to modulate viral proteins. This approach could be rapidly adapted to new and emerging viruses. The first method built and studied a virus-host-physical interaction network; a three-layer multimodal network of drug target proteins, human protein-protein interactions, and viral-host protein-protein interactions. The second method evaluated sequence similarity between viral proteins and other proteins, visualized by constructing a virus-host-similarity interaction network. Methods were validated on the human immunodeficiency virus, hepatitis B, hepatitis C, and human papillomavirus, then deployed on SARS-CoV-2. Comparison of virus-host-physical interaction predictions to known antiviral drugs had AUCs of 0.69, 0.59, 0.78, and 0.67, respectively, reflecting that the scores are predictive of effective drugs. For SARS-CoV-2, 569 candidate drugs were predicted, of which 37 had been included in clinical trials for SARS-CoV-2 (AUC = 0.75, P-value 3.21 × 10-3). As further validation, top-ranked candidate antiviral drugs were analyzed for binding to protein targets in silico; binding scores generated by BindScope indicated a 70% success rate.

Flavonoids from Pterogyne nitens as Zika virus NS2B-NS3 protease inhibitors

Although the widespread epidemic of Zika virus (ZIKV) and its neurological complications are well-known there are still no approved drugs available to treat this arboviral disease or vaccine to prevent the infection. Flavonoids from Pterogyne nitens have already demonstrated anti-flavivirus activity, although their target is unknown. In this study, we virtually screened an in-house database of 150 natural and semi-synthetic compounds against ZIKV NS2B-NS3 protease (NS2B-NS3p) using docking-based virtual screening, as part of the OpenZika project. As a result, we prioritized three flavonoids from P. nitens, quercetin, rutin and pedalitin, for experimental evaluation. We also used machine learning models, built with Assay Central® software, for predicting the activity and toxicity of these flavonoids. Biophysical and enzymatic assays generally agreed with the in silico predictions, confirming that the flavonoids inhibited ZIKV protease. The most promising hit, pedalitin, inhibited ZIKV NS2B-NS3p with an IC50 of 5 μM. In cell-based assays, pedalitin displayed significant activity at 250 and 500 µM, with slight toxicity in Vero cells. The results presented here demonstrate the potential of pedalitin as a candidate for hit-to-lead (H2L) optimization studies towards the discovery of antiviral drug candidates to treat ZIKV infections.

Overview of antiviral drug candidates targeting coronaviral 3C-like main proteases.

Coronaviruses (CoVs) are positive single-stranded RNA viruses that cause severe respiratory syndromes in humans, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Coronavirus disease 2019 (COVID-19) caused by a novel severe acute respiratory syndrome CoV (SARS-CoV-2) at the end of 2019 became a global pandemic. The 3C-like cysteine protease (3CLpro) processes viral polyproteins to yield mature non-structural proteins, thus playing an important role in the CoV life cycle, and therefore is considered as a prominent target for antiviral drugs. To date, many 3CLpro inhibitors have been reported, and their molecular mechanisms have been illustrated. Here, we briefly introduce the structural features of 3CLpro of the human-related SARS-CoV, MERS-CoV and SARS-CoV-2, and explore the potency and mechanism of their cognate inhibitors. This information will shed light on the development and optimization of CoV 3CLpro inhibitors, which may benefit the further designation of therapeutic strategies for treating CoV diseases.

Identification of FDA Approved Antiviral Drugs for COVID-19 Treatment using Unbiased Virtual Screening

COVID-19 has led to a worldwide pandemic and treatments are limited and only used in severe cases. This study aims to identify FDA-approved antiviral drugs for the inhibition of host proteins of ACE2 and TMPRSS2 and key SARS-CoV-2 proteins of Mpro, NSP15, RBD of S protein, and RdRp domain of NSP12 for potential COVID-19 treatment through unbiased virtual screening. To reduce the bias of using a single molecular docking program for virtual screening, we used three docking programs, AutoDock Vina, AutoDock4, and RosettaLigand, and adopted unbiased rank-by-rank scoring method to identify top FDA-approved antiviral drug candidates for each receptor protein, which could be repurposed for potential COVID-19 treatment.

5-amino levulinic acid inhibits SARS-CoV-2 infection in vitro

The current COVID-19 pandemic requires urgent development of effective therapeutics. 5-amino levulinic acid (5-ALA) is a naturally synthesized amino acid and has been used for multiple purposes including as an anticancer therapy and as a dietary supplement due to its high bioavailability. In this study, we demonstrated that 5-ALA treatment potently inhibited infection of SARS-CoV-2, a causative agent of COVID-19, in cell culture. The antiviral effects could be detected in both human and non-human cells, without significant cytotoxicity. Therefore, 5-ALA is worth to be further investigated as an antiviral drug candidate for COVID-19.

Recent Advances in the Synthesis of β-Carboline Alkaloids.

β-Carboline alkaloids are a remarkable family of natural and synthetic indole-containing heterocyclic compounds and they are widely distributed in nature. Recently, these alkaloids have been in the focus of interest, thanks to their diverse biological activities. Their pharmacological activity makes them desirable as sedative, anxiolytic, hypnotic, anticonvulsant, antitumor, antiviral, antiparasitic or antimicrobial drug candidates. The growing potential inherent in them encourages many researchers to address the challenges of the synthesis of natural products containing complex β-carboline frameworks. In this review, we describe the recent developments in the synthesis of β-carboline alkaloids and closely related derivatives through selected examples from the last 5 years. The focus is on the key steps with improved procedures and synthetic approaches. Furthermore the pharmacological potential of the alkaloids is also highlighted.

Host cell glutamine metabolism as a potential antiviral target.

A virus minimally contains a nucleic acid genome packaged by a protein coat. The genome and capsid together are known as the nucleocapsid, which has an envelope containing a lipid bilayer (mainly phospholipids) originating from host cell membranes. The viral envelope has transmembrane proteins that are usually glycoproteins. The proteins in the envelope bind to host cell receptors, promoting membrane fusion and viral entry into the cell. Virus-infected host cells exhibit marked increases in glutamine utilization and metabolism. Glutamine metabolism generates ATP and precursors for the synthesis of macromolecules to assemble progeny viruses. Some compounds derived from glutamine are used in the synthesis of purines and pyrimidines. These latter compounds are precursors for the synthesis of nucleotides. Inhibitors of glutamine transport and metabolism are potential candidate antiviral drugs. Glutamine is also an essential nutrient for the functions of leukocytes (lymphocyte, macrophage, and neutrophil), including those in virus-infected patients. The increased glutamine requirement for immune cell functions occurs concomitantly with the high glutamine utilization by host cells in virus-infected patients. The development of antiviral drugs that target glutamine metabolism must then be specifically directed at virus-infected host cells to avoid negative effects on immune functions. Therefore, the aim of this review was to describe the landscape of cellular glutamine metabolism to search for potential candidates to inhibit glutamine transport or glutamine metabolism.

Chemically sulfated arabinoxylans from Plantago ovata seed husk: Synthesis, characterization and antiviral activity

Limited options for the treatments of diseases triggered through viral infections revealed the quest for novel antiviral drugs. Polysaccharide sulfates owing to their unique mode of action are prominent antiviral drug candidates. Herein, the arabinoxylan of Plantago ovata seed husk was simultaneously extracted and chemically sulfated using sulphur trioxide-pyridine reagent in N,N-dimethylformamide solvent (SO3⋅Py/DMF). Thus, three arabinoxylan sulfates (IS1201–IS1203) holding variable degrees of sulfation (DS: 0.1–0.9), molar masses (18.4–31.3 kDa) and glycosyl makeup (Ara: Xyl::10–19:81–90; molar ratio) were produced and then characterized. According to the results, these polymers displayed anti-herpes simplex virus type 1 activity and their potency depends upon DS. The utmost effective compound (IS1203, IC50: 2.9 μg mL−1) was a 18.4 kDa arabinoxylan possessing sulfate groups at O-3 and O-2,3 positions of xylopyranosyl (Xylp), and O-5 of arabinofuranosyl (Araf) residues. Besides, this polymer showed no cytotoxicity at concentration up to 1000 μg mL−1. Given that polysaccharide sulfates have antiviral activities, synthesis of new molecules possessing diverse structures will be a useful addition to the arsenal of antivirals.

Potential inhibitors of SARS-CoV-2 (COVID 19) spike protein of the delta and delta plus variant: In silico studies of medicinal plants of North-East India

Phytochemicals of 38 Medicinal plants of North-East India, with anti-viral, anti-oxidant or anti-bacterial properties were screened for properties of drug likeness. 231 phytochemicals were screened with LIPINSKI rule of five to obtain 131 candidates, which were further screened with SWISS-ADME, to obtain 50 phytochemicals. These phytochemicals were docked with the spike protein of the Delta variant (B.1.617.2) and Delta-Plus (AY.1) variant of SARS-CoV-2 using Autodock Vina and MOE 09. The target proteins were constructed by homology modeling using Swiss-Model. Hydroxychloroquine, taken as a standard in docking analysis, exhibited a binding energy of −6.5 ​kcal/mol and −6.1 ​kcal/mol with respect to the Delta variant and Delta-Plus variant respectively. Among the 50 docked results most flavones showed very good docking scores. 3,5,8-Trimethoxy-6,7,4,5-bis(methylenedioxy)flavone, a Poly-Methoxyflavone, produced a highest docking score of −8.7 ​kcal/mol with respect to both the spike protein targets. Poly-Methoxyflavones and Poly-Ethoxyflavones exhibited good binding affinity for the target spike protein of SARS-CoV-2, and can be potential anti-viral drug candidates against the existing Delta variant of the SARS-CoV-2.

Insights into bioinformatic approaches for repurposing compounds as anti-viral drugs.

BackgroundDrug repurposing is a cost-effective strategy to identify drugs with novel effects. We searched for drugs exhibiting inhibitory activity to Herpes Simplex virus 1 (HSV-1). Our strategy utilized gene expression data generated from HSV-1-infected cell cultures which was paired with drug effects on gene expression. Gene expression data from HSV-1 infected and uninfected neurons were analyzed using BaseSpace Correlation Engine (Illumina®). Based on the general Signature Reversing Principle (SRP), we hypothesized that the effects of candidate antiviral drugs on gene expression would be diametrically opposite (negatively correlated) to those effects induced by HSV-1 infection.ResultsWe initially identified compounds capable of inducing changes in gene expression opposite to those which were consequent to HSV-1 infection. The most promising negatively correlated drugs (Valproic acid, Vorinostat) did not significantly inhibit HSV-1 infection further in African green monkey kidney epithelial cells (Vero cells). Next, we tested Sulforaphane and Menadione which showed effects similar to those caused by viral infections (positively correlated). Intriguingly, Sulforaphane caused a modest but significant inhibition of HSV-1 infection in Vero cells (IC50 = 180.4 µM, p = 0.008), but exhibited toxicity when further explored in human neuronal progenitor cells (NPCs) derived from induced pluripotent stem cells.ConclusionsThese results reveal the limits of the commonly used SRP strategy when applied to the identification of novel antiviral drugs and highlight the necessity to refine the SRP strategy to increase its utility.

Repurposing potential of FDA‐approved and investigational drugs for COVID‐19 targeting SARS‐CoV‐2 spike and main protease and validation by machine learning algorithm

The present study aimed to assess the repurposing potential of existing antiviral drug candidates (FDA-approved and investigational) against SARS-CoV-2 target proteins that facilitates viral entry and replication into the host body. To evaluate molecular affinities between antiviral drug candidates and SARS-CoV-2 associated target proteins such as spike protein (S) and main protease (Mpro ), a molecular interaction simulation was performed by docking software (MVD) and subsequently the applicability score was calculated by machine learning algorithm. Furthermore, the STITCH algorithm was used to predict the pharmacology network involving multiple pathways of active drug candidate(s). Pharmacophore features of active drug(s) molecule was also determined to predict structure-activity relationship (SAR). The molecular interaction analysis showed that cordycepin has strong binding affinities with S protein (-180) and Mpro proteins (-205) which were relatively highest among other drug candidates used. Interestingly, compounds with low IC50 showed high binding energy. Furthermore, machine learning algorithm also revealed high applicability scores (0.42-0.47) of cordycepin. It is worth mentioning that the pharmacology network depicted the involvement of cordycepin in different pathways associated with bacterial and viral diseases including tuberculosis, hepatitis B, influenza A, viral myocarditis, and herpes simplex infection. The embedded pharmacophore features with cordycepin also suggested strong SAR. Cordycepin's anti-SARS-CoV-2 activity indicated 65% (E-gene) and 42% (N-gene) viral replication inhibition after 48h of treatment. Since, cordycepin has both preclinical and clinical evidences on antiviral activity, in addition the present findings further validate and suggest repurposing potential of cordycepin against COVID-19.

Stopping Membrane-Enveloped Viruses with Nanotechnology Strategies: Toward Antiviral Drug Development and Pandemic Preparedness.

Membrane-enveloped viruses are a leading cause of viral epidemics, and there is an outstanding need to develop broad-spectrum antiviral strategies to treat and prevent enveloped virus infections. In this review, we critically discuss why the lipid membrane surrounding enveloped virus particles is a promising antiviral target and cover the latest progress in nanotechnology research to design and evaluate membrane-targeting virus inhibition strategies. These efforts span diverse topics such as nanomaterials, self-assembly, biosensors, nanomedicine, drug delivery, and medical devices and have excellent potential to support the development of next-generation antiviral drug candidates and technologies. Application examples in the areas of human medicine and agricultural biosecurity are also presented. Looking forward, research in this direction is poised to strengthen capabilities for virus pandemic preparedness and demonstrates how nanotechnology strategies can help to solve global health challenges related to infectious diseases.

\u03b2-arrestin 2 as an activator of cGAS-STING signaling and target of viral immune evasion

Virus infection may induce excessive interferon (IFN) responses that can lead to host tissue injury or even death. β-arrestin 2 regulates multiple cellular events through the G protein-coupled receptor (GPCR) signaling pathways. Here we demonstrate that β-arrestin 2 also promotes virus-induced production of IFN-β and clearance of viruses in macrophages. β-arrestin 2 interacts with cyclic GMP-AMP synthase (cGAS) and increases the binding of dsDNA to cGAS to enhance cyclic GMP-AMP (cGAMP) production and the downstream stimulator of interferon genes (STING) and innate immune responses. Mechanistically, deacetylation of β-arrestin 2 at Lys171 facilitates the activation of the cGAS–STING signaling and the production of IFN-β. In vitro, viral infection induces the degradation of β-arrestin 2 to facilitate immune evasion, while a β-blocker, carvedilol, rescues β-arrestin 2 expression to maintain the antiviral immune response. Our results thus identify a viral immune-evasion pathway via the degradation of β-arrestin 2, and also hint that carvedilol, approved for treating heart failure, can potentially be repurposed as an antiviral drug candidate.