Drug-resistant Virus Research Articles

Physicochemical and sequence determinants of antiviral peptides.

Antiviral peptides (AVPs) open new possibilities as an effective antiviral therapeutic in the current scenario of evolving drug-resistant viruses. Knowledge about the sequence and structure activity relationship in AVPs is still largely unknown. AVPs and antimicrobial peptides (AMPs) share several common features but as they target different life forms (living organisms and viruses), exploring the differential sequence features may facilitate in designing specific AVPs. The current work developed accurate prediction models for discriminating (a) AVPs from AMPs, (b) Coronaviridae AVPs from other virus family specific AVPs and (c) highly active AVPs (HAA) from lowly active AVPs (LAA). Further explainable machine learning methods (using model agnostic global interpretable methods) are utilized for exploring and interpreting the physicochemical spaces of AVPs, Coronaviridae AVPs and highly active AVPs. To further understand the association of physicochemical space distribution with pIC50 values, regression models were developed and analyzed using accumulated local effects and interaction strength analysis. An independent sample t-test is used to filter out the significant compositional differences between the smaller length HAA and longer length HAA groups. AVPs prefer lower charge/length ratio and basic residues in comparison with AMPs. Coronaviridae family-specific AVPs have lower propensities for basic amino acids, charge and preference for aspartic acid. Further there is prevalence for basic residues in lowly active AVPs as compared to highly active AVPs. Sequence order effects captured in terms of average amino acid pair distances proved to be more constructive in deciphering the sequences of AVPs.

Sticklac-Derived Natural Compounds Inhibiting RNase H Activity of HIV-1 Reverse Transcriptase.

The emergence of drug-resistant viruses is a serious concern in current chemotherapy for human immunodeficiency virus type-1 (HIV-1) infectious diseases. Hence, antiviral drugs aiming at targets that are different from those of approved drugs are still required, and the RNase H activity of HIV-1 reverse transcriptase is a suitable target. In this study, a search of a series of natural compounds was performed to identify the RNase H inhibitors. Three compounds were found to block the RNase H enzymatic activity. A laccaic acid skeleton was observed in all three natural compounds. A hydroxy phenyl group is connected to an anthraquinone backbone in the skeleton. An acetamido-ethyl, amino-carboxy-ethyl, and amino-ethyl are bound to the phenyl in laccaic acids A, C, and E, respectively. Laccaic acid C showed a 50% inhibitory concentration at 8.1 μM. Laccaic acid C also showed inhibitory activity in a cell-based viral proliferation assay. Binding structures of these three laccaic acids were determined by X-ray crystallographic analysis using a recombinant protein composed of the HIV-1 RNase H domain. Two divalent metal ions were located at the catalytic center in which one carbonyl and two hydroxy groups on the anthraquinone backbone chelated two metal ions. Molecular dynamics simulations were performed to examine the stabilities of the binding structures. Laccaic acid C showed the strongest binding to the catalytic site. These findings will be helpful for the design of potent inhibitors with modification of laccaic acids to enhance the binding affinity.

Apigenin's Therapeutic Potential Against Viral Infection.

Several antiviral drugs are clinically approved to treat influenza that is a highly prevalent acute respiratory disease. However, emerging drug-resistant virus strains undermine treatment efficacy, highlighting the exigency for novel antiviral drugs to counter these drug-resistant strains. Plants and their derivates have been historically utilized as medicinal remedies, and extensive studies have evidenced the antiviral potential of phytochemicals. Notably, apigenin is a predominant flavonoid with minimal toxicity and substantial therapeutic effects in various disease models. Despite its many anti-inflammatory, anti-oxidant, anti-cancer, anti-bacterial, and other beneficial bioactivities, existing reviews have yet to focus on apigenin's antiviral effects. Therefore, this review elucidates apigenin's therapeutic and antiviral properties in vitro and in vivo, discussing its mode of action and future prospects. Apigenin's remarkable inhibition by modulating multiple mechanisms against viruses has promising potential for novel plant-derived antiviral drugs and further clinical study developments.

Recommendations on data sharing in HIV drug resistance research.

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

FFMAVP: a new classifier based on feature fusion and multitask learning for identifying antiviral peptides and their subclasses.

Antiviral peptides (AVPs) are widely found in animals and plants, with high specificity and strong sensitivity to drug-resistant viruses. However, due to the great heterogeneity of different viruses, most of the AVPs have specific antiviral activities. Therefore, it is necessary to identify the specific activities of AVPs on virus types. Most existing studies only identify AVPs, with only a few studies identifying subclasses by training multiple binary classifiers. We develop a two-stage prediction tool named FFMAVP that can simultaneously predict AVPs and their subclasses. In the first stage, we identify whether a peptide is AVP or not. In the second stage, we predict the six virus families and eight species specifically targeted by AVPs based on two multiclass tasks. Specifically, the feature extraction module in the two-stage task of FFMAVP adopts the same neural network structure, in which one branch extracts features based on amino acid feature descriptors and the other branch extracts sequence features. Then, the two types of features are fused for the following task. Considering the correlation between the two tasks of the second stage, a multitask learning model is constructed to improve the effectiveness of the two multiclass tasks. In addition, to improve the effectiveness of the second stage, the network parameters trained through the first-stage data are used to initialize the network parameters in the second stage. As a demonstration, the cross-validation results, independent test results and visualization results show that FFMAVP achieves great advantages in both stages.

Mathematical analysis of a multiscale hepatitis C virus infection model with two viral strains

Direct-acting antiviral agents (DAAs) have shown higher cure rates for treating hepatitis C virus (HCV) by directly interfering with different steps of the HCV life cycle. To optimize drug combinations and accurately quantify the antiviral effect of DAAs treatments, mathematical models should include the intracellular virus replication processes. In this study, we develop a two-strain multiscale age-structured model that includes intracellular viral RNA replication and extracellular viral infection. We prove the existence, positivity, and boundedness of the solution, and derive the conditions for the existence and stability of the three steady states (non-infection steady state, boundary steady state, and coexistence steady state). Under certain biologically reasonable assumptions, we obtain the approximate solutions of the viral load decline of the two virus strains (sensitive and drug-resistant virus strains) during treatment, and the long-term approximation is shown to be in good agreement with the solution of the original model. We also carry out numerical simulations using the long-term approximate solution, providing insights into the influence of antiviral effects on the viral load change of the two virus strains during treatment with DAAs.

TRIM5α restricts poxviruses and is antagonized by CypA and the viral protein C6.

Human tripartite motif protein 5α (TRIM5α) is a well-characterized restriction factor for some RNA viruses, including HIV1-5; however, reports are limited for DNA viruses6,7. Here we demonstrate that TRIM5α also restricts orthopoxviruses and, via its SPRY domain, binds to the orthopoxvirus capsid protein L3 to diminish virus replication and activate innate immunity. In response, several orthopoxviruses, including vaccinia, rabbitpox, cowpox, monkeypox, camelpox and variola viruses, deploy countermeasures. First, the protein C6 binds to TRIM5 via the RING domain to induce its proteasome-dependent degradation. Second, cyclophilin A (CypA) is recruited via interaction with the capsid protein L3 to virus factories and virions to antagonize TRIM5α; this interaction is prevented by cyclosporine A (CsA) and the non-immunosuppressive derivatives alisporivir and NIM811. Both the proviral effect of CypA and the antiviral effect of CsA are dependent on TRIM5α. CsA, alisporivir and NIM811 have antiviral activity against orthopoxviruses, and because these drugs target a cellular protein, CypA, the emergence of viral drug resistance is difficult. These results warrant testing of CsA derivatives against orthopoxviruses, including monkeypox and variola.

Frequency of drug resistance and immune escape mutations in the hepatitis B virus genome detected in pregnant women in the Republic of Guinea

The aim of the work is to assess the prevalence of hepatitis B virus drug resistance mutations and immune escape mutations in pregnant women in the Republic of Guinea.
 Materials and methods. Blood plasma samples obtained from 480 pregnant women from different regions of the Republic of Guinea with laboratory-confirmed viral hepatitis B were studied. Nucleotide sequences for genotype identification and mutation detection were obtained using nested-PCR followed by Sanger sequencing, based on overlapping pairs of primers spanning the complete genome of the virus.
 Results and discussion. In the examined group, the viral genotype E was the most prevalent (92.92%) compared with subgenotypes A1 (1.67%), A3 (1.46%), D1 (0.63%), D2 (1.04%) and D3 (2.29%). Among the examined HBV-infected pregnant women, 188 (39.17%) had undetectable HBsAg. Drug resistance mutations were detected in 33 individuals, which amounted to 6.88%. The following mutations were found: S78T (27.27%), L80I (24.24%), S202I (15.15%), M204I/V (42.42%). The presence of polymorphic variants not described as drug resistant has also been shown in positions associated with the development of drug resistance to tenofovir, lamivudine, telbivudine and entecavir (L80F, S202I, M204R). When analyzing the MHR and the region of a determinant, mutations were detected in 318 (66.25%) of pregnant women. In 172 of them, which amounted to 54.09%, multiple mutations were found. The amino acid substitutions in 13 positions associated with HBsAg-negative hepatitis B and/or potentially affecting HBsAg antigenicity were identified.
 Conclusion. The high prevalence of immune escape and drug resistance mutations potentially associated with false-negative result of HBsAg screening, prophylaxis failure, and virological failure of therapy that has been identified among treatment naive pregnant women imposes a serious problem.

Changes of Viral Load, Drug Resistance, and CD4 Cell Count in HIV-1-Infected Patients Receiving Antiretroviral Therapy in Hebei Province, China, 2003-2019.

In this study, a total of 462 samples of whole blood were collected from 36 patients enrolled. During the entire course of antiretroviral therapy (ART) from 2003 to 2019, both the CD4 cell count and viral load (VL) of study patients were examined annually, and an HIV-1 genotypic drug resistance (DR) assay was carried out using an in-house method when the HIV-1 VL was >1,000 copies/mL. The results indicated that 13 (36.1%) experienced treatment failure and 23 (63.9%) experienced treatment success among 36 patients. The proportion of patients with effective treatment after the adjustment of ART regimens was significantly higher than before adjustment (χ2 = 33.796, p < .001). Furthermore, the frequencies of HIV-1 DR mutations before adjustment were higher than those after adjustment (t = 3.345, p = .002). In particular, among 23 patients with effective treatment after adjustment, the means ± standard deviations of the VLs and CD4 cell counts before adjustment were 3.85 ± 0.65 log RNA copies/mL and 226.83 ± 106.06 cells/mm3, respectively, compared with 2.19 ± 0.58 log RNA copies/mL and 367.68 ± 174.62 cells/mm3, respectively, after adjustment. Obviously, there were statistically significant differences in the changes in VL (t = 8.728, p < .001) and CD4 cell count (t = -4.476, p < .001) before and after adjustment. Therefore, patients who received updated ART regimens containing LPV/r and TDF after adjustment achieved better therapeutic effects compared with patients who received initial ART regimens harboring D4T/AZT or NVP. This suggests that future research is needed to initiate the surveillance of DR, VLs, and CD4 cell counts immediately after HIV diagnosis, and dynamic changes in these indicators so as to optimize ART effects.

Discovery of ligustrazine and chalcone derivatives as novel viral nucleoprotein nuclear export inhibitors against influenza viruses.

Influenza viruses pose a significant threat to human health worldwide due to seasonal epidemics and occasional global pandemics. These viruses can cause severe upper respiratory tract infections that contribute to high morbidity and mortality rates. The emergence of drug-resistant influenza viruses has created the need for the development of novel broad-spectrum antivirals. Here, we present a novel anti-influenza agent with new targets and mechanisms of action to address this problem. Our findings led to the discovery of a novel influenza virus inhibitor, a ligustrazine derivative known as A9. We have found that it exhibits broad-spectrum antiviral properties against influenza A and B viruses (IAV and IBV, respectively), including oseltamivir-resistant strain. Through multiple bioassays such as time-of-addition assay, indirect immunofluorescence assay, and nuclear-cytoplasmic fractionation assay, we demonstrated that A9 inhibits the nuclear export of the viral ribonucleoprotein (vRNP). Furthermore, escape mutant analyses and affinity studies determined by surface plasmon resonanceindicated that A9 specifically targets the nucleoprotein.In addition, four chalcone derivatives developed from A9 (B14, B29, B31, and B32), were found to effectively inhibit the replication of influenza virus through the same mechanism of action. In this manuscript we highlight A9 and its four derivatives as potential leads for the treatment of IAV and IBV infections, and their unique and novel mechanism of action probable benefit the field of anti-influenza drug discovery.

Genetic characterization of HIV-1 viruses among cases with antiretroviral therapy failure in Suzhou City, China

BackgroundThis retrospective study aimed to characterize the distribution of HIV-1 genotypes and the prevalence of drug resistance mutations in people with antiretroviral treatment (ART) failure in Suzhou City, China.MethodsPol gene of HIV-1 viruses in blood samples of EDTA anticoagulants from 398 patients with failed antiviral treatment was successfully amplified by using an in-house assay. Drug resistance mutations were analyzed by using the Stanford HIV Drug Resistance Database system (https://hivdb.stanford.edu/hivdb/by-mutations/). HIV-1 genotypes were determined by the REGA HIV subtyping tool (version 3.46, https://www.genomedetective.com/app/typingtool/hiv). Near full-length genomes (NFLG) of HIV-1 viruses were obtained by next generation sequencing method.ResultsSequences analysis of the pol gene revealed that CRF 01_AE (57.29%, 228/398) was the dominant subtype circulating in Suzhou City, followed by CRF 07_BC (17.34%, 69/398), subtype B (7.54%, 30/398), CRF 08_BC (6.53%, 26/398), CRF 67_01B (3.02%, 12/398) and CRF55_01B (2.51%, 10/398). The overall prevalence of drug-resistant mutations in cases with ART failure was 64.57% (257/398), including 45.48% (181/398) for nucleotide reverse transcriptase inhibitors (NRTIs) mutations, 63.32% (252/398) for non-nucleoside reverse transcriptase inhibitors (NNRTIs) mutations, and 3.02% (12/398) for protease inhibitors (PIs) mutations. Ten near full-length genomes (NFLG) of HIV-1 viruses were identified, including six recombinants of CRF 01_AE and subtype B, two recombinants of CRF 01_AE, subtype B and subtype C sequences, one recombinant of CRF 01_AE and subtype C and one recombinant of CRF 01_AE, subtype A1 and subtype C.ConclusionsThe high prevalence of drug-resistant HIV-1 viruses was a serious challenge for HIV prevention and treatment of people with HIV infection. Treatment regimens for ART failure patients should be adjusted over time based on the outcome of drug resistance tests. NFLG sequencing facilitates the identification of new recombinants of HIV-1.

Age and CD4+ T cell counts are inversely associated with HIV drug resistance mutations in treatment naive female sex workers.

The increasing prevalence of human immunodeficiency virus (HIV) drug resistance mutations (HIVDRM) in untreated seropositive persons has consequences for future treatment options. This is extremely important in key populations such as female sex workers (FSWs), where the prevalence of pretreatment drug resistance (PDR) and associated risk factors are unknown. In this study, we analyzed PDR and associated risk factors in recently diagnosed and treatment-naive FSWs in Nairobi, Kenya. In this cross-sectional study, we used 64 HIV-seropositive plasma samples collected from FSWs between November 2020 and April 2021. To identify HIVDRM, the pol gene was amplified and genotyped using sanger sequencing. The effects of age, tropism, CD4+ T cell count, subtype, and location on HIVDRM counts were examined using Poisson regression. Overall, the prevalence of PDR was 35.9% (95% CI: 24.3-48.9), which was strongly influenced by K103N and M184V mutations, which confer resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTI), respectively. Subtype A1 was predominant followed by subtype D with a notable increase in inter-subtype recombinants. We found statistically significant evidence that age was inversely related to HIVDRM. A FSW who is 1 year older had 12% less HIVDRM (incidence rate ratios [IRR]: 0.88; 95% CI: 0.82-0.95; P < .001), after adjusting for CD4+ T cell count, subtype, location, and tropism. Similarly, an increase in CD4+ T cell count by 1 unit, was associated with 0.4% fewer HIVDRM (IRR: 0.996; 95% CI: 0.994-0.998; P = .001), while controlling for the other variables. HIV-1 tropism was not associated with HIVDRM counts. In conclusion, our findings show a high prevalence of NNRTIs. Lower CD4+ T cell counts and younger age were significant risk factors that influenced HIVDRM loads. This finding underscores the relevance of targeted interventions and the importance of continuing to focus on FSWs as a way of addressing the HIV epidemic.

Factors Associated With Viral Suppression and Drug Resistance in Children and Adolescents Living With HIV in Care and Treatment Programs in Southern Tanzania.

Achieving viral suppression (VS) for persons living with HIV is key to reaching epidemic control. We assessed the prevalence of VS and the frequency of HIV drug resistance mutations (HIVDRM) among children and adolescents living with HIV (CALHIV) in the Southern Highland zone of Tanzania. From 2019 to 2021, we enrolled CALHIV aged 1-19 years on ART for >6 months in a cross-sectional study. Participants had viral load (VL) testing; those with VL ≥ 1000 copies/mL underwent HIVDRM testing. VS (<1000 copies/mL) prevalence estimates were calculated and robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for associations with potential predictors of VS. Of 707 participants, 595 had VS (PR: 0.84, 95% CI: 0.81-0.87). Use of an integrase strand transfer inhibitor-containing regimen (aPR 1.15, 95% CI: 0.99-1.34), age 5-9 years (aPR 1.16, 95% CI: 1.07-1.26), and seeking care at a referral center (aPR 1.12, 95% CI: 1.04-1.21) were associated with VS. Factors inversely associated with VS included having one (aPR 0.82, 95% CI: 0.72-0.92) or two or more (aPR 0.79, 95% CI: 0.66-0.94) referrals for adherence counselling, and self-reporting missing one to two (aPR 0.88, 95% CI: 0.78-0.99) or three or more (aPR 0.77, 95% CI: 0.63-0.92) doses of ART in the past month. Of 74 participants with PRRT and INT sequencing done, 60 (81.1%) had HIVDRMs at the following frequencies: 71.6%, 67.6%, 1.4%, and 4.1% for major NNRTI, NRTI, PI, and INSTI respectively. Higher rates of VS were observed in this cohort, and HIVDRMs were common in those without VS. This evidence supports ART optimization using dolutegravir-based regimens. However, better strategies to improve adherence are needed.

HIV-1 genotypic profiling ensures effective response to third-line antiretroviral therapy in Cameroon.

In order to limit the emergence of human immunodeficiency virus (HIV) drug resistance in a context of limited antiretroviral options, we sought to evaluate the efficacy of third-line (3L) regimens considering HIV genotypic resistance profile at initiation of 3L in Cameroon. A cohort-study was conducted from January-September 2020 among patients initiating a 3L antiretroviral therapy regimen at the Yaoundé Central Hospital. HIV-1 protease-reverse transcriptase was sequenced at the Chantal Biya international reference center for research on HIV/AIDS prevention and management and results were interpreted using Stanford HIVdbv8.3. Good virological response (viral load < 390 copies/mL) was assessed after 12 months using OPP-ERA platform. Statistical analyses were performed using Epi Info v7.2.2.6, with P < .05 considered statistically significant. Of the 38 patients initiating 3L with an available genotyping (42% female; median age, 49 [39-57] years), median cluster of differentiation type 4 count and viral load were 173 [34-374] cells/μL and 169,322 [30,382-551,826] copies/mL, respectively. At enrollment, all patients harbored resistance to reverse transcriptase inhibitors and 66% (25/38) to protease-inhibitors, although 63% (24/38) were still susceptible to darunavir/ritonavir. Preferred 3L regimen was dolutegravir + darunavir/r + tenofovir + lamivudine (51%) and median duration on 3L was 21 [17-32] months. Interestingly, 82% (31/38) of the participants achieved good virological response on 3L, regardless of genotypic profile at recruitment, variations in 3L regimens (P = .9) and baseline cluster of differentiation type 4 count (P = .3). Despite the high burden of reverse transcriptase inhibitor - and protease inhibitor boosted by ritonavir drug resistance, genotyping-guided 3L regimens is accompanied by virological success in most patients. This high efficacy, most likely due to use of high genetic barrier antiretrovirals, requires continuous adherence support alongside close monitoring for long-term effectiveness in similar programmatic settings.

Influence of siRNA complexes on the reproduction of influenza A virus (Orthomyxoviridae: Alphainfluenzavirus) in vivo

Influenza is one of the most pressing global health problems. Despite the wide range of available anti-influenza drugs, the viral drug resistance is an increasing concern and requires the search for new approaches to overcome it. A promising solution is the development of drugs with action that is based on the inhibition of the activity of cellular genes through RNA interference. Evaluation in vivo of the preventive potential of miRNAs directed to the cellular genes FLT4, Nup98 and Nup205 against influenza infection. The A/California/7/09 strain of influenza virus (H1N1) and BALB/c mice were used in the study. The administration of siRNA and experimental infection of animals were performed intranasally. The results of the experiment were analyzed using molecular genetic and virological methods. The use of siRNA complexes Nup98.1 and Nup205.1 led to a significant decrease in viral reproduction and concentration of viral RNA on the 3rd day after infection. When two siRNA complexes (Nup98.1 and Nup205.1) were administered simultaneously, a significant decrease in viral titer and concentration of viral RNA was also noted compared with the control groups. The use of siRNAs in vivo can lead to an antiviral effect when the activity of single or several cellular genes is suppressed. The results indicate that the use of siRNAs targeting the cellular genes whose expression products are involved in viral reproduction is one of the promising methods for the prevention and treatment of not only influenza, but also other respiratory infections.

Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in female Syrian hamsters and retains partial susceptibility to treatment

The SARS-CoV-2 main protease (3CLpro) is one of the promising therapeutic targets for the treatment of COVID-19. Nirmatrelvir is the first 3CLpro inhibitor authorized for treatment of COVID-19 patients at high risk of hospitalization. We recently reported on the in vitro selection of SARS-CoV-2 3CLpro resistant virus (L50F-E166A-L167F; 3CLprores) that is cross-resistant with nirmatrelvir and other 3CLpro inhibitors. Here, we demonstrate that the 3CLprores virus replicates efficiently in the lungs of intranasally infected female Syrian hamsters and causes lung pathology comparable to that caused by the WT virus. Moreover, hamsters infected with 3CLprores virus transmit the virus efficiently to co-housed non-infected contact hamsters. Importantly, at a dose of 200 mg/kg (BID) of nirmatrelvir, the compound was still able to reduce the lung infectious virus titers of 3CLprores-infected hamsters by 1.4 log10 with a modest improvement in the lung histopathology as compared to the vehicle control. Fortunately, resistance to Nirmatrelvir does not readily develop in clinical setting. Yet, as we demonstrate, in case drug-resistant viruses emerge, they may spread easily which may thus impact therapeutic options. Therefore, the use of 3CLpro inhibitors in combination with other drugs may be considered, especially in immunodeficient patients, to avoid the development of drug-resistant viruses.

Superlattice Nanofilm on a Touchscreen for Photoexcited Bacteria and Virus Killing by Tuning Electronic Defects in the Heterointerface.

Currently, the global COVID-19 pandemic has significantly increased the public attention toward the spread of pathogenic viruses and bacteria on various high-frequency touch surfaces. Developing a self-disinfecting coating on a touchscreen is an urgent and meaningful task. Superlattice materials are among the most promising photocatalysts owing to their efficient charge transfer in abundant heterointerfaces. However, excess electronic defects at the heterointerfaces result in the loss of substantial amounts of photogenerated charge carrier. In this study, a ZnOFe2 O3 superlattice nanofilm is designed via atomic layer deposition for photocatalytic bactericidal and virucidal touchscreen. Additionally, electronic defects in the superlattice heterointerface are engineered. Photogenerated electrons and holes will be rapidly separated and transferred into ZnO and Fe2 O3 across the heterointerfaces owing to the formation of ZnO, FeO, and ZnFe covalent bonds at the heterointerfaces, where ZnO and Fe2 O3 function as electronic donors and receptors, respectively. The high generation capacity of reactive oxygen species results in a high antibacterial and antiviral efficacy (>90%) even against drug-resistant bacteria and H1N1 viruses under simulated solar or low-power LED light irradiation. Meanwhile, this superlattice nanofilm on a touchscreen shows excellent light transmission (>90%), abrasion resistance (106 times the round-trip friction), and biocompatibility.

Harnessing the Noncanonical Keap1-Nrf2 Pathway for Human Cytomegalovirus Control.

Host-derived cellular pathways can provide an unfavorable environment for virus replication. These pathways have been a subject of interest for herpesviruses, including the betaherpesvirus human cytomegalovirus (HCMV). Here, we demonstrate that a compound, ARP101, induces the noncanonical sequestosome 1 (SQSTM1)/p62-Keap1-Nrf2 pathway for HCMV suppression. ARP101 increased the levels of both LC3 II and SQSTM1/p62 and induced phosphorylation of p62 at the C-terminal domain, resulting in its increased affinity for Keap1. ARP101 treatment resulted in Nrf2 stabilization and translocation into the nucleus, binding to specific promoter sites and transcription of antioxidant enzymes under the antioxidant response element (ARE), and HCMV suppression. Knockdown of Nrf2 recovered HCMV replication following ARP101 treatment, indicating the role of the Keap1-Nrf2 axis in HCMV inhibition by ARP101. SQSTM1/p62 phosphorylation was not modulated by the mTOR kinase or casein kinase 1 or 2, indicating ARP101 engages other kinases. Together, the data uncover a novel antiviral strategy for SQSTM1/p62 through the noncanonical Keap1-Nrf2 axis. This pathway could be further exploited, including the identification of the responsible kinases, to define the biological events during HCMV replication. IMPORTANCE Antiviral treatment for human cytomegalovirus (HCMV) is limited and suffers from the selection of drug-resistant viruses. Several cellular pathways have been shown to modulate HCMV replication. The autophagy receptor sequestosome 1 (SQSTM1)/p62 has been reported to interact with several HCMV proteins, particularly with components of HCMV capsid, suggesting it plays a role in viral replication. Here, we report on a new and unexpected role for SQSTM1/p62, in HCMV suppression. Using a small-molecule probe, ARP101, we show SQSTM1/p62 phosphorylation at its C terminus domain initiates the noncanonical Keap1-Nrf2 axis, leading to transcription of genes under the antioxidant response element, resulting in HCMV inhibition in vitro. Our study highlights the dynamic nature of SQSTM1/p62 during HCMV infection and how its phosphorylation activates a new pathway that can be exploited for antiviral intervention.

Lamivudine induced pure red cell aplasia and HIV-1 drug resistance-associated mutations: a case report

Adverse effects linked to antiretroviral therapy (ART) may contribute to poor adherence on the patient's side. Consequently, human immunodeficiency virus (HIV) drug resistance mutations could emerge, negatively impacting the body's immune system. Meanwhile, severe immunosuppression can lead to several conditions, including anemia. The cause of anemia in HIV infection is multifactorial, and can be mainly explained by deleterious direct effects of the virus on the bone marrow, and opportunistic infections such as Parvovirus B19. Other causes include blood loss resulting from neoplasms and gastrointestinal lesions. Moreover, anemia can also be caused by antiretroviral drugs. We report a case of persistent anemia after ART initiation, kidney injury and treatment failure following a lengthy period of non-adherence to ART. The anemia was classified as Pure Red Cell Aplasia (PRCA). With treatment modification, the anemia resolved and the patient attained virologic suppression. Lamivudine (3TC) was pointed out as the cause of PRCA, which resolved after its withdrawal from the ART regimen. This rare side effect should be investigated in patients on 3TC who present with recurrent anemia.

Erratum: A Review of Marine Natural Product Resources with Potential Bioactivity Against SARS-COV-2

The emergence of new pathogenic viruses and the constant outbreak of viral diseases have created an upsurge in novel antiviral agents. Marine natural products are the most unexplored reservoir of novel, biologically active, chemically diverse compounds. A systematic literature review was conducted using PRISMA guidelines, accessing four major databases; PubMed, Science Direct, Scopus, and Google Scholar. Numerous studies supported the robust antiviral activity of marine resources against drug-resistant viruses such as SARS, Ebola, Influenza, and HIV. However, adequate research on marine resources for developing anti-covid therapy is lacking. The aim of the review was to explore the marine resources and their compounds that could lead to developing an effective antiviral drug. We also highlighted the current status of novel compounds against different species of corona family and discussed the future prospects of marine resources against COVID-19 management.