4-(3-Phenylsulfonylindol-2-yl)-1-(pyridin-2-yl)piperazinyl-methanones as Potent Inhibitors of both SARS-CoV-2 and HCoV-OC43 Viruses.

SARS-CoV-2 and HCoV-OC43 belong to the same ß genus of the Coronaviridae family. SARS-CoV-2 was responsible for the recent COVID-19 pandemic, and HCoV-OC43 is the etiological agent of mild upper respiratory tract infections. SARS-COV-2 and HCoV-OC43 co-infections were found in children with respiratory symptoms during the COVID-19 pandemic. The two ß-coronaviruses share a high degree of homology between the 3CLpro active sites, so much so that the safer HCoV-OC43 has been suggested as a tool for the identification of new anti-SARS-COV-2 agents. Compounds 5 and 24 inhibited effectively both Wuhan and British SARS-CoV-2 patient isolates in Vero E6 cells and the HCoV-OC43 in MRC-5 cells at low micromolar concentrations. The inhibition was apparently exerted via targeting the 3CLpro active sites of both viruses. Compounds 5 and 24 at 100 µM inhibited the SARS-CoV-2 3CLpro activity of 61.78 and 67.30%, respectively. These findings highlight 5 and 24 as lead compounds of a novel class of antiviral agents with the potential to treat SARS-COV-2 and HCoV-OC43 infections.

Inhibition of porcine reproductive and respiratory syndrome virus replication by rifampicin in vitro.

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause significant economic losses to the global swine industry, yet effective prevention and control measures remain elusive. The development of novel antivirals is thus urgently needed. Rifampicin (RFP), a semisynthetic derivative of rifamycin, has been previously reported to inhibit the replication of certain mammalian DNA viruses as well as RNA viruses. In this study, we unveil RFP as a potent inhibitor of PRRSV both in Marc-145 cells (half-maximal inhibitory concentration 61.26 µM) and porcine alveolar macrophages (half-maximal inhibitory concentration 53.09 µM). The inhibitory effect of RFP occurred during viral replication rather than binding, internalization and release. We also demonstrated that RFP inhibits PRRSV proteins production in the early stage of infection, without inhibiting host protein synthesis. Moreover, RFP effectively restricted porcine epidemic diarrhea virus (PEDV) and porcine enteric alphacoronavirus (PEAV) infection in Vero cells. In summary, these findings indicate the promising potential of RFP as a therapeutic agent for PRRSV, PEDV and PEAV infection in pig farms.

[Effects of inhibitors of DNA repair enzymes OGG1 and MTH1 on the replication of African swine fever virus].

African swine fever virus (ASFV), as a contagious viral pathogen, is responsible for the occurrence of African swine fever (ASF), a rapidly spreading and highly lethal disease. Since ASFV was introduced into China in 2018, it has been quickly spread to many provinces, which brought great challenges to the pig industry in China. Due to the limited knowledge about the pathogenesis of ASFV, neither vaccines nor antiviral drugs are available. We have found that ASFV infection can induce oxidative stress responses in cells, and DNA repair enzymes play a key role in this process. This study employed RNA interference, RT-qPCR, Western blotting, Hemadsorption (HAD), and flow cytometry to investigate the effects of the inhibitors of DNA repair enzymes OGG1 and MTH1 on ASFV replication and evaluated the anti-ASFV effects of the inhibitors. This study provides reference for the development of anti-viral drugs.

Combined Effect of Basic Antiherpetic Drugs with a New Inhibitor of the Terminase Complex of Herpes Simplex Virus Type 1 in Vero Cell Cultures.

Carriers of herpes simplex virus type 1 (HSV-1) account for more than 90% of the global population. Infection manifests itself in the formation of blisters and ulcers on the face or genitals and can cause blindness, encephalitis, and generalized infection. All first- and second-line modern antiherpetic drugs selectively inhibit viral DNA polymerase. The purine-benzoxazine conjugate LAS-131 ((S)-4-[6-(purin-6-yl)aminohexanoyl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine), which we have described earlier, uses the large subunit of the HSV-1 terminase complex as a biotarget and selectively inhibits HSV-1 reproduction in vitro. Basically new results were for the first time obtained to characterize the combined effect on human herpesvirus infection for LAS-131 used in combination with practically significant antiviral compounds, including the nucleoside analogs acyclovir (ACV), penciclovir (PCV), ganciclovir (GCV), brivudine (BVdU), iododeoxyuridine (IdU), and adenine arabinoside (Ara-A); the nucleoside phosphonate analog cidofovir (CDV); and the pyrophosphate analog foscarnet (FOS). A cytopathic effect (CPE) inhibition assay showed that the drug concentration that inhibited the virus-induced CPE by 50% decreased by a factor of 2 (an additive effect, FOS) or more (a synergistic effect; ACV, PCV, GCV, IdU, BVdU, Ara-A, and CDV) when the drugs were used in combination with LAS-131. Nonpermissive conditions for HSV-1 reproduction were thus created at lower drug concentrations, opening up new real possibilities to control human herpesvirus infection.

Picroside II disrupts IBDV replication via targeting VP1 polymerase.

Infectious bursal disease virus (IBDV) is a highly contagious virus with a dsRNA genome, predominantly infecting chickens and causing significant economic losses due to high mortality rates. The emergence of recombinant, novel variant, and highly virulent strains that evade current vaccines has led to frequent epidemics and outbreaks in the poultry industry. The lack of targeted antivirals for IBDV underscores the pressing requirement to develop potent therapeutic options. Within this framework, our research investigated the effectiveness of picroside II, a naturally derived iridoid glycoside, against viruses in DF-1 cells. Our findings demonstrate that picroside II significantly inhibits viral replication, with its efficacy increasing proportionally to the dosage administered. Through time-addition and antiviral duration analysis, we determined that picroside II therapeutically blocks IBDV replication, with its effects persisting for over 72 hours. Further investigation revealed that picroside II specifically inhibits the cellular replication stage of IBDV's lifecycle. Additionally, our findings indicate that picroside II impairs VP1 polymerase activity by binding to the active pocket, which significantly disrupts the interaction between VP1 and VP3. Mutations at three critical binding sites on VP1 not only impair virus replication but also hinder polymerase function and disrupt VP1-VP3 interactions. Collectively, these results demonstrate that picroside II, by inhibiting viral polymerase activity, represents a promising antiviral agent against IBDV.

Flow analysis-solid phase extraction system and UHPLC-MS/MS analytical methodology for the determination of antiviral drugs in surface water.

An automated flow analysis-solid phase extraction (FA-SPE) system and methodology of ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) analysis were developed for the determination of selected antiviral drugs (acyclovir, amantadine, rimantadine, and oseltamivir) in water samples. The proposed FA-SPE approach enables the integration of various extraction stages and elimination of the sample evaporation step and offers individual customisation of SPE parameters, inter alia sample, and eluate flow rate and volume. Using the developed FA-SPE procedure, e.g. a 100-fold preconcentration of the target analytes in 1 h was achieved. A method for chromatographic analysis was also developed to determine the selected antiviral drugs in combination with the use of the FA-SPE system. The developed FA-SPE UHPLC-MS/MS method was validated including the determination of linearity of analytical graphs, limits of detection (5.5-99.9 pg mL-1) and quantification (18.3-329.8 pg mL-1), intra-day (1.8-8.3%) and inter-day (3.0-9.2%) precision, recovery (95.6-105.3%), and matrix effects (- 12.9 to 13.2%). The proposed method was successfully applied to analyse tap, drinking, and river water samples, revealing the presence of amantadine at a concentration of 40.1 pg mL-1 in one sample. The environmental impact of the developed FA-SPE sample preparation procedure was also assessed using the AGREEprep metric tool and compared with five other literature methods, achieving the most sustainable outcome.

A glimpse into viral warfare: decoding the intriguing role of highly pathogenic coronavirus proteins in apoptosis regulation.

Coronaviruses employ various strategies for survival, among which the activation of endogenous or exogenous apoptosis stands out, with viral proteins playing a pivotal role. Notably, highly pathogenic coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV exhibit a greater array of non-structural proteins compared to low-pathogenic strains, facilitating their ability to induce apoptosis via multiple pathways. Moreover, these viral proteins are adept at dampening host immune responses, thereby bolstering viral replication and persistence. This review delves into the intricate interplay between highly pathogenic coronaviruses and apoptosis, systematically elucidating the molecular mechanisms underpinning apoptosis induction by viral proteins. Furthermore, it explores the potential therapeutic avenues stemming from apoptosis inhibition as antiviral agents and the utilization of apoptosis-inducing viral proteins as therapeutic modalities. These insights not only shed light on viral pathogenesis but also offer novel perspectives for cancer therapy.

Repurposing Antiviral Drugs as Potential Anti-EGFR Agents in NSCLC: A Structure-Based Screening and Molecular Dynamics Analysis.

One of the problems resulting from recurrent hyperactivated or mutant epidermal growth factor receptors (EGFR) in non-small cell lung cancer (NSCLC) is therapeutic resistance. Consequently, this leads to increased expression of oncogenic proteins and reduces the efficacy of EGFR tyrosine kinase inhibitors (TKIs). This study assessed antiviral drug efficacy as potential anti-EGFR agents for NSCLC. We used structure-based virtual screening to evaluate 66 antiviral drugs thoroughly. The top 6 antiviral drugs exhibiting impressive binding energies  (i.e. surpassing a threshold of -8.5 kcalmol-1) were identified. Subsequent bioactivity analysis and ADMET profiling were performed to select the most promising candidates, followed by a molecular dynamic simulation. Among the selected antiviral regimens, dolutegravir demonstrated the highest docking score (-9.8 kcalmol-1), followed by rilpivirine and ensitrelvir, surpassing other candidates and our reference EGFR TKI. Further molecular dynamics simulations revealed promising dynamic interactions of dolutegravir, ensitrelvir, and rilpivirine with the EGFR target as compared with afatinib. Our findings highlight the repositioning potential of antiviral drugs for anti-EGFR drug discovery, supported by their robust docking scores, ADMET profiles, dynamic interactions, and binding free energies. The results open up new avenues for advanced NSCLC therapy. Further in vitro investigations are warranted to evaluate their efficacy and safety.

Recent advances in photocatalytic removal of antiviral drugs by Z-scheme and S-scheme heterojunction.

The possible impact of antivirals on ecosystems and the emergence of antiviral resistance are the reasons for concern about their environmental release. Consequently, there has been a significant increase in curiosity regarding their presence in both organic and synthetic systems in recent years. The primary objective of this review is to address the void of information regarding the global presence of antiviral drugs in both wastewater and natural water sources. Photocatalytic degradation of pollutants is an eco-friendly, cost-effective method that effectively addresses environmental degradation. The development of efficient photocatalysts remains a significant issue in accelerating the degradation of pollutants, especially when employing solar light. Thus, the development of Z-scheme and S-scheme semiconductor heterojunctions has emerged as a viable method to improve light absorption and enhance the redox capability of photocatalysts. The principles of Z-scheme and S-scheme are reviewed extensively. The degradation route and occurrence of antiviral are discussed briefly. Finally, a short preview of the degradation of antiviral using Z-scheme and S-scheme is also highlighted.

Nanovesicles as Potential Carriers for Delivery of Antiviral Drugs: A Comprehensive Review.

Different nanocarriers-based strategies are now extensively being used as an important strategy for improving drug efficacy and responsiveness, reducing toxicity issues related to drugs and harmful side effects, and overcoming the numerous significant difficulties related to absorption and bioavailability. Amongst different nanocarriers, nanovesicles are excellent and versatile systems for effectively delivering biomolecules, drugs, and targeted ligand distribution and location. Nanovesicles are nanosized self-assembling spherical capsules with an aqueous core and one/more lipid(s) layers. Several synthetic nanovesicles have been developed and investigated for their prospective uses in delivering drugs, proteins, peptides, nutrients, etc. Important procedures for nanovesicle manufacturing are thin-film hydration, unshaken method, ethanol injection, ether injection, proliposomes, freeze-drying, hot method, cold method, reverse-phase evaporation, and ultrasonication. Liposomes, liposomes, ethosomes, exosomes, and transferosomes (elastic vesicles) are the nonvesicular candidates extensively investigated to deliver antiviral drugs. This review article comprehensively reviews different nanovesicles, their compositions, manufacturing, and applications as potential carriers for effectively delivering different antiviral drugs to treat viral diseases.

Early use of oral antiviral drugs and the risk of post COVID-19 syndrome: A systematic review and network meta-analysis.

OBJECTIVES: This study aimed to determine the association of early use of oral antiviral drugs (including nirmatrelvir-ritonavir and molnupiravir) with the risk of post COVID-19 condition (PCC) and compare the possible efficacy of nirmatrelvir-ritonavir and molnupiravir. METHODS: PubMed, Web of Science, Embase, Cochrane, MedRxiv, and Psycinfo were searched from inception until November 1, 2023. We included studies that assessed the effect of oral antiviral drugs on the incidence of PCC. Pairwise and network meta-analyses were conducted using a random-effects model. Risk ratios (RRs) for oral antiviral drugs were calculated with a confidence interval (CI). RESULTS: Nine observational studies containing 866,066 patients were included. Nirmatrelvir-ritonavir and molnupiravir were evaluated in eight and two studies respectively, with both drugs evaluated in one study. Pair-wise meta-analysis showed that early oral antiviral drugs reduced PCC risk (RR 0.77, 95% CI 0.68-0.88). Network meta-analysis showed that nirmatrelvir-ritonavir may perform better than molnupiravir (surface under the cumulative ranking curve: 95.5% vs. 31.6%) at reducing PCC risk. CONCLUSIONS: Early use of oral antiviral drugs may potentially protect against developing PCC in non-hospitalized patients with COVID-19. These findings support the standardized administration of oral antiviral drugs in patients during the acute phase of COVID-19 according to the guidelines.

Novel transcription and replication-competent virus-like particles system modelling the Nipah virus life cycle.

Nipah virus (NiV), a highly pathogenic Henipavirus in humans, has been responsible for annual outbreaks in recent years. Experiments involving live NiV are highly restricted to biosafety level 4 (BSL-4) laboratories, which impedes NiV research. In this study, we developed transcription and replication-competent NiV-like particles (trVLP-NiV) lacking N, P, and L genes. This trVLP-NiV exhibited the ability to infect and continuously passage in cells ectopically expressing N, P, and L proteins while maintaining stable genetic characteristics. Moreover, the trVLP-NiV displayed a favourable safety profile in hamsters. Using the system, we found the NiV nucleoprotein residues interacting with viral RNA backbone affected viral replication in opposite patterns. This engineered system was sensitive to well-established antiviral drugs, innate host antiviral factors, and neutralizing antibodies. We then established a high-throughput screening platform utilizing the trVLP-NiV, leading to the identification of tunicamycin as a potential anti-NiV compound. Evidence showed that tunicamycin inhibited NiV replication by decreasing the infectivity of progeny virions. In conclusion, this trVLP-NiV system provided a convenient and versatile molecular tool for investigating NiV molecular biology and conducting antiviral drug screening under BSL-2 conditions. Its application will contribute to the development of medical countermeasures against NiV infections.

QSPR/QSAR study of antiviral drugs modeled as multigraphs by using TI's and MLR method to treat COVID-19 disease.

The ongoing COVID-19 pandemic continues to pose significant challenges worldwide, despite widespread vaccination. Researchers are actively exploring antiviral treatments to assess their efficacy against emerging virus variants. The aim of the study is to employ M-polynomial, neighborhood M-polynomial approach and QSPR/QSAR analysis to evaluate specific antiviral drugs including Lopinavir, Ritonavir, Arbidol, Thalidomide, Chloroquine, Hydroxychloroquine, Theaflavin and Remdesivir. Utilizing degree-based and neighborhood degree sum-based topological indices on molecular multigraphs reveals insights into the physicochemical properties of these drugs, such as polar surface area, polarizability, surface tension, boiling point, enthalpy of vaporization, flash point, molar refraction and molar volume are crucial in predicting their efficacy against viruses. These properties influence the solubility, permeability, and bio availability of the drugs, which in turn affect their ability to interact with viral targets and inhibit viral replication. In QSPR analysis, molecular multigraphs yield notable correlation coefficients exceeding those from simple graphs: molar refraction (MR) (0.9860), polarizability (P) (0.9861), surface tension (ST) (0.6086), molar volume (MV) (0.9353) using degree-based indices, and flash point (FP) (0.9781), surface tension (ST) (0.7841) using neighborhood degree sum-based indices. QSAR models, constructed through multiple linear regressions (MLR) with a backward elimination approach at a significance level of 0.05, exhibit promising predictive capabilities highlighting the significance of the biological activity I C 50 (Half maximal inhibitory concentration). Notably, the alignment of predicted and observed values for Remdesivir's with obs p I C 50 = 6.01 ,pred p I C 50 = 6.01 ( p I C 50 represents the negative logarithm of I C 50 ) underscores the accuracy of multigraph-based QSAR analysis. The primary objective is to showcase the valuable contribution of multigraphs to QSPR and QSAR analyses, offering crucial insights into molecular structures and antiviral properties. The integration of physicochemical applications enhances our understanding of factors influencing antiviral drug efficacy, essential for combating emerging viral strains effectively.

Advancements in Antiviral Drug Development: Comprehensive Insights into Design Strategies and Mechanisms Targeting Key Viral Proteins.

Viral infectious diseases have always been a threat to human survival and quality of life, impeding the stability and progress of human society. As such, researchers have persistently focused on developing highly efficient, low-toxicity antiviral drugs, whether for acute or chronic infectious diseases. This article presents a comprehensive review of the design concepts behind virus-targeted drugs, examined through the lens of antiviral drug mechanisms. The intention is to provide a reference for the development of new, virus-targeted antiviral drugs and guide their clinical usage.

Matrine exhibits antiviral activities against PEDV by directly targeting Spike protein of the virus and inducing apoptosis via the MAPK signaling pathway.

Porcine Epidemic Diarrhea Virus (PEDV) is a highly contagious virus that causes Porcine Epidemic Diarrhea (PED). This enteric disease results in high mortality rates in piglets, leading to significant financial losses in the pig industry. However, vaccines cannot provide sufficient protection against epidemic strains. Spike (S) protein exposed on the surface of virion mediates PEDV entry into cells. Our findings imply that matrine (MT), a naturally occurring alkaloid, inhibits PEDV infection targeting S protein of virions and biological process of cells. The GLY434 residue in the autodocking site of the S protein and MT conserved based on sequence comparison. This study provides a comprehensive analysis of viral attachment, entry, and virucidal effects to investigate how that MT inhibits virus replication. MT inhibits PEDV attachment and entry by targeting S protein. MT was added to cells before, during, or after infection, it exhibits anti-PEDV activities and viricidal effects. Network pharmacology focuses on addressing causal mechanisms rather than just treating symptoms. We identified the key genes and screened the cell apoptosis involved in the inhibition of MT on PEDV infection in network pharmacology. MT significantly promotes cell apoptosis in PEDV-infected cells to inhibit PEDV infection by activating the MAPK signaling pathway. Collectively, we provide the biological foundations for the development of single components of traditional Chinese medicine to inhibit PEDV infection and spread.

A comparative study of different antiviral treatment protocols in HCV related cryoglobulinemic vasculitis.

The treatment of HCV and its sequelae are used to be predominantly based on Interferon (IFN). However, this was associated with significant adverse events as a result of its immunostimulant capabilities. Since their introduction, the directly acting antiviral drugs (DAAs), have become the standard of care to treat of HCV and its complications including mixed cryoglobulinemic vasculitis (MCV). In spite of achieving sustained viral response (SVR), there appeared many reports describing unwelcome complications such as hepatocellular and hematological malignancies as well as relapses. Prolonged inflammation induced by a multitude of factors, can lead to DNA damage and affects BAFF and APRIL, which serve as markers of B-cell proliferation. We compared, head-to-head, three antiviral protocols for HCV-MCV treatment As regards the treatment response and relapse, levels of BAFF and APRIL among pegylated interferon α-based and free regimens (Sofosbuvir + Ribavirin; SOF-RIBA, Sofosbuvir + Daclatasvir; SOF-DACLA). Regarding clinical response HCV-MCV and SVR; no significant differences could be identified among the 3 different treatment protocols, and this was also independent form using IFN. We found no significant differences between IFN-based and free regimens DNA damage, markers of DNA repair, or levels of BAFF and APRIL. However, individualized drug-to-drug comparisons showed many differences. Those who were treated with IFN-based protocol showed decreased levels of DNA damage, while the other two IFN-free groups showed increased DNA damage, being the worst in SOF-DACLA group. There were increased levels of BAFF through follow-up periods in the 3 protocols being the best in SOF-DACLA group (decreased at 24 weeks). In SOF-RIBA, CGs relapsed significantly during the follow-up period. None of our patients who were treated with IFN-based protocol had significant clinico-laboratory relapse. Those who received IFN-free DAAs showed a statistically significant relapse of constitutional manifestations. Our findings suggest that IFN-based protocols are effective in treating HCV-MCV similar to IFN-free protocols. They showed lower levels of DNA damage and repair. We believe that our findings may offer an explanation for the process of lymphoproliferation, occurrence of malignancies, and relapses by shedding light on such possible mechanisms.

Efficacy and safety of carrimycin in ten patients with severe pneumonia following solid organ transplantation.

BACKGROUND: The number of patients undergoing solid organ transplantation has increased annually. However, infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of immunosuppressants. Carrimycin is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4''-O-isovaleryltransferase gene (ist) from streptomyces thermotoleran. Carrimycin has good antibacterial and antiviral effects. However, no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia (SP) after solid organ transplantation. AIM: To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical treatment. METHODS: In March 2022, ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March 2022. When the condition was critical and difficult to control with other drugs, carrimycin was administered. These ten patients' clinical features and treatment protocols were retrospectively analyzed, and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were evaluated. RESULTS: All ten patients were included in the analysis. Regarding etiological agent detection, there were three cases of fungal pneumonia, two cases of bacterial pneumonia, two cases of Pneumocystis pneumonia, and three cases of mixed infections. After treatment with carrimycin, the disease in seven patients significantly improved, the course of the disease was significantly shortened, fever was quickly controlled, chest computed tomography was significantly improved, and oxygenation was significantly improved. Finally, the patients were discharged after curing. One patient died of acute respiratory distress syndrome, and two patients discontinued treatment. CONCLUSION: Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation. Carrimycin may have antibacterial and antiviral effects in patients with SP following solid organ transplantation.

N-Heterocycles as Promising Antiviral Agents: A Comprehensive Overview.

Viruses are a real threat to every organism at any stage of life leading to extensive infections and casualties. N-heterocycles can affect the viral life cycle at many points, including viral entrance into host cells, viral genome replication, and the production of novel viral species. Certain N-heterocycles can also stimulate the host's immune system, producing antiviral cytokines and chemokines that can stop the reproduction of viruses. This review focused on recent five- or six-membered synthetic N-heterocyclic molecules showing antiviral activity through SAR analyses. The review will assist in identifying robust scaffolds that might be utilized to create effective antiviral drugs with either no or few side effects.

Pathogenesis of COVID19 and the applications of US FDA-approved repurposed antiviral drugs to combat SARS-CoV-2 in Saudi Arabia: A recent update by review of literature.

Still, there is no cure for the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused coronavirus disease 2019 (COVID19). The COVID19 pandemic caused health emergencies which resulted in enormous medical and financial consequences worldwide including Saudi Arabia. Saudi Arabia is the largest Arab country of the Middle East. The urban setting of Saudi Arabia makes it vulnerable towards SARS-CoV-2 (SCV-2). Religious areas of this country are visited by millions of pilgrims every year for the Umrah and Hajj pilgrimage, which contributes to the potential COVID19 epidemic risk. COVID19 throws various challenges to healthcare professionals to choose the right drugs or therapy in clinical settings because of the lack of availability of newer drugs. Current drug development and discovery is an expensive, complex, and long process, which involves a high failure rate in clinical trials. While repurposing of United States Food and Drug Administration (US FDA)-approved antiviral drugs offers numerous benefits including complete pharmacokinetic and safety profiles, which significantly shorten drug development cycles and reduce costs. A range of repurposed US FDA-approved antiviral drugs including ribavirin, lopinavir/ritonavir combination, oseltamivir, darunavir, remdesivir, nirmatrelvir/ritonavir combination, and molnupiravir showed encouraging results in clinical trials in COVID19 treatment. In this article, several COVID19-related discussions have been provided including emerging variants of concern of, COVID19 pathogenesis, COVID19 pandemic scenario in Saudi Arabia, drug repurposing strategies against SCV-2, as well as repurposing of US FDA-approved antiviral drugs that might be considered to combat SCV-2 in Saudi Arabia. Moreover, drug repurposing in the context of COVID19 management along with its limitations and future perspectives have been summarized.