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Antiviral Res 2021 May 1:105081. Epub 2021 May 1.

Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, People's Republic of China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, People's Republic of China; Research Center for African Swine Fever Prevention and Control, South China Agricultural University, Guangzhou, People's Republic of China; National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China. Electronic address:

African swine fever virus (ASFV) is a highly infectious and lethal swine pathogen that causes serious socio-economic consequences in endemic countries for which no safe and effective vaccine is currently available. GS-441524, a 1-cyano-substituted adenine C-nucleoside ribose analogue, inhibits viral RNA transcription by competing with natural nucleosides (ATP, TTP, CTP, and GTP) and effectively inhibits viral RNA-dependent RNA polymerase activity. However, whether GS-441524 can inhibit the replication of DNA viruses is unknown. Read More

Antiviral Res 2021 Apr 29:105080. Epub 2021 Apr 29.

Baruch S. Blumberg Institute, Doylestown, Pennsylvanian, USA. Electronic address:

Assembly of hepatitis B virus (HBV) capsids is driven by the hydrophobic interaction of core protein (Cp) at dimer-dimer interface. Binding of core protein allosteric modulators (CpAMs) to a hydrophobic "HAP" pocket formed between the inter-dimer interface strengths the dimer-dimer interaction and misdirects the assembly of Cp dimers into non-capsid Cp polymers or morphologically normal capsids devoid of viral pregenomic (pg) RNA and DNA polymerase. In this study, we performed a systematic mutagenesis analysis to identify Cp amino acid residues at Cp dimer-dimer interface that are critical for capsid assembly, pgRNA encapsidation and resistance to CpAMs. Read More

Antiviral Res 2021 Apr 29:105079. Epub 2021 Apr 29.

- State Research Center of Virology and Biotechnology "Vector" Rospotrebnadzor, Koltsovo, Novosibirsk Region, 630559, Russian Federation.

This study aimed to assess the antiviral susceptibility of influenza A(H5N8) viruses isolated in Russia in 2014-2018. Genetic analysis of 57 Russian isolates with full genome sequences did not find any markers of reduced susceptibility to baloxavir. Only one strain bore an amino acid substitution associated with adamantane resistance (M2-S31N). Read More

Antiviral Res 2021 Apr 21;190:105078. Epub 2021 Apr 21.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China. Electronic address:

Antiviral therapeutics is one effective avenue to control and end this devastating COVID-19 pandemic. The viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 has been recognized as a valuable target of antivirals. However, the cell-free SARS-CoV-2 RdRp biochemical assay requires the conversion of nucleotide prodrugs into the active triphosphate forms, which regularly occurs in cells yet is a complicated multiple-step chemical process in vitro, and thus hinders the utility of this cell-free assay in the rapid discovery of RdRp inhibitors. Read More

Antiviral Res 2021 Apr 19;190:105073. Epub 2021 Apr 19.

Pós-graduação em Ciências Aplicadas da Saúde do Adulto, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Ambulatório de Hepatites Virais, Instituto Alfa de Gastroenterologia, Hospital Das Clínicas / Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address:

The HCV treatment with DAAs has offered a unique opportunity to analyze the changes in the immune system caused by the rapid inhibition of viral replication. We sought to analyze the kinetics profiles of serum biomarkers (LuminexTM) in fifty patients with chronic hepatitis C enrolled in a longitudinal investigation carried out before (baseline), during (W2-4 and W8-12 weeks) and post-treatment (W12-24 weeks) with sofosbuvir plus daclatasvir or simeprevir. The results demonstrated a clear biomarker overproduction in HCV patients at baseline. Read More

Antiviral Res 2021 Apr 17;190:105075. Epub 2021 Apr 17.

College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China; Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China; Qingdao Academy of Chinese Medicinal Sciences, Shandong University of Traditional Chinese Medicine, Qingdao, 266122, China. Electronic address:

The emerging SARS-CoV-2 infection is the cause of the global COVID-19 pandemic. To date, there are limited therapeutic options available to fight this disease. Here we examined the inhibitory abilities of two broad-spectrum antiviral natural products chebulagic acid (CHLA) and punicalagin (PUG) against SARS-CoV-2 viral replication. Read More

Antiviral Res 2021 Apr 16;190:105074. Epub 2021 Apr 16.

Department of Medical Sciences, Clinical Microbiology, Uppsala University, Uppsala, Sweden. Electronic address:

Tick-borne encephalitis (TBE) is a severe neurological disorder caused by tick-borne encephalitis virus (TBEV), a member of the Flavivirus genus. Currently, two vaccines are available in Europe against TBEV. However, TBE cases have been rising in Sweden for the past twenty years, and thousands of cases are reported in Europe, emphasizing the need for antiviral treatments against this virus. Read More

Antiviral Res 2021 Apr 15;190:105076. Epub 2021 Apr 15.

Key Laboratory of Medical Molecular Virology, Department of Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai, China; Songjiang District Central Hospital, Shanghai, China. Electronic address:

Chronic infection of hepatitis B virus (HBV) is a high risk factor for hepatic diseases, such as liver fibrosis, cirrhosis and hepatocellular carcinoma. Non-responders and hyporesponders to HBV vaccine are not protected from HBV infection. Patients that achieve autonomous or treatment-induced recovery are at risk of reactivation due to persistence of HBV covalently closed circular DNA (cccDNA) in hepatocytes. Read More

Antiviral Res 2021 Apr 14:105077. Epub 2021 Apr 14.

Department of Pediatrics, Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, Virginia, 23298-0163. Electronic address:

Broad-spectrum antivirals are more needed than ever to provide treatment options for novel emerging viruses and for viruses that lack therapeutic options or have developed resistance. A large number of viruses rely on charge-dependent non-specific interactions with heparan sulfate (HS), a highly sulfated glycosaminoglycan (GAG), for attachment to cell surfaces to initiate cell entry. As such, inhibitors targeting virion-HS interactions have potential to have broad-spectrum antiviral activity. Read More

Antiviral Res 2021 Mar 26;190:105064. Epub 2021 Mar 26.

Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases 'L. Spallanzani' IRCCS, Rome, Italy; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy. Electronic address:

COVID-19 is currently a highly pressing health threat and therapeutic strategies to mitigate the infection impact are urgently needed. Characterization of the SARS-CoV-2 interactome in infected cells may represent a powerful tool to identify cellular proteins hijacked by viruses for their life cycle and develop host-oriented antiviral therapeutics. Here we report the proteomic characterization of host proteins interacting with SARS-CoV-2 Nucleoprotein in infected Vero E6 cells. Read More

Antiviral Res 2021 May 16;189:105063. Epub 2021 Mar 16.

Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea. Electronic address:

Romidepsin, a histone deacetylase (HDAC) inhibitor, has been approved for the treatment of relapsed and refractory peripheral T-cell lymphoma. However the use of romidepsin reportedly causes potent EBV (Epstein-Barr virus) reactivation leading to severe adverse events in patients with natural killer (NK)/T-cell lymphoma (NKTL). As inhibition of EBV lytic cycle reactivation may help prevent romidepsin-induced adverse events in NKTL, we herein set out to identify a safe and effective drug for inhibiting EBV reactivation and examine its mechanism of inhibition. Read More

Antiviral Res 2021 May 13;189:105062. Epub 2021 Mar 13.

Department of Molecular Medicine, University of Padua, Padua, Italy. Electronic address:

We recently reported that some clinically approved antifungal drugs are potent inhibitors of human cytomegalovirus (HCMV). Here, we report the broad-spectrum activity against HCMV of isavuconazole (ICZ), a new extended-spectrum triazolic antifungal drug. ICZ inhibited the replication of clinical isolates of HCMV as well as strains resistant to the currently available DNA polymerase inhibitors. Read More

Antiviral Res 2021 May 11;189:105057. Epub 2021 Mar 11.

Department of Life Sciences and Systems Biology, 10123, Turin, Italy. Electronic address:

Emergence of drug resistance and adverse effects often affect the efficacy of nucleoside analogues in the therapy of Herpes simplex type 1 (HSV-1) and type 2 (HSV-2) infections. Host-targeting antivirals could therefore be considered as an alternative or complementary strategy in the management of HSV infections. To contribute to this advancement, here we report on the ability of a new generation inhibitor of a key cellular enzyme of de novo pyrimidine biosynthesis, the dihydroorotate dehydrogenase (DHODH), to inhibit HSV-1 and HSV-2 in vitro replication, with a potency comparable to that of the reference drug acyclovir. Read More

Antiviral Res 2021 May 10;189:105060. Epub 2021 Mar 10.

Department of Viroscience, Erasmus Medical Center, Rotterdam, 3015GE, the Netherlands; Department of Pediatrics, Subdivision Infectious Diseases and Immunology, Erasmus Medical Center - Sophia, Rotterdam, the Netherlands. Electronic address:

Amino acid substitutions in influenza virus neuraminidase (NA) that cause resistance to neuraminidase inhibitors (NAI) generally result in virus attenuation. However, influenza viruses may acquire secondary substitutions in the NA and hemagglutinin (HA) proteins that can restore viral fitness. To assess to which extent this happens, the emergence of NAI resistance substitutions and secondary - potentially compensatory - substitutions was quantified in influenza viruses of immunocompetent individuals included in the Influenza Resistance Information Study (IRIS; NCT00884117). Read More

Antiviral Res 2021 05 10;189:105055. Epub 2021 Mar 10.

CNR-IBF, Istituto di Biofisica, Via Celoria 26, I-20133, Milano, Italy; Dipartimento di Bioscienze, Università di Milano, Via Celoria 26, I-20133, Milano, Italy. Electronic address:

The current emergency of the novel coronavirus SARS-CoV2 urged the need for broad-spectrum antiviral drugs as the first line of treatment. Coronaviruses are a large family of viruses that already challenged humanity in at least two other previous outbreaks and are likely to be a constant threat for the future. In this work we developed a pipeline based on in silico docking of known drugs on SARS-CoV1/2 RNA-dependent RNA polymerase combined with in vitro antiviral assays on both SARS-CoV2 and the common cold human coronavirus HCoV-OC43. Read More

Antiviral Res 2021 May 9;189:105058. Epub 2021 Mar 9.

Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China. Electronic address:

Multidrug-resistance hepatitis B virus (MDR HBV), defined as those with mutations resistant to both nucleoside analogs lamivudine/telbivudine/entecavir (LAM/LdT/ETV) and nucleotide analog adefovir (ADV), has potential to cause treatment difficulty. To clarify clinical prevalence and virological features of MDR HBV, we investigated serum samples from 28,236 chronic HBV-infected patients with treatment of nucleoside/nucleotide analogs. All patients underwent resistance testing in the Fifth Medical Center of Chinese PLA General Hospital between 2007 and 2019. Read More

Antiviral Res 2021 May 10;189:105037. Epub 2021 Mar 10.

State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Background: Whether different serum HBV RNA detection assays can consistently predict treatment outcomes in patients with chronic hepatitis B remains controversial.

Methods: We enrolled 188 patients who had stopped nucleos(t)ide analogues (NAs) (STOP cohort-1, -2) and 78 receiving entecavir (ETV) therapy (ETV cohort) and used double-target (targeting both 5' and 3' ends of the HBV pregenome RNA [DT-RNA]) and three single-target (targeting the S-region [S-RNA], X-region [X-RNA], and poly-A tail of HBV RNA [PolyA-RNA]) assays to predict treatment outcomes.

Results: In STOP cohorts, DT-RNA, S-RNA and X-RNA at NAs cessation showed higher predictive powers for clinical relapse (time-dependent areas under the curve [AUCs] for years 1, 2, 3, and 4 ranged between 0. Read More

Antiviral Res 2021 05 10;189:105056. Epub 2021 Mar 10.

National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India. Electronic address:

Emetine is a FDA-approved drug for the treatment of amebiasis. Previously we demonstrated the antiviral efficacy of emetine against some RNA and DNA viruses. In this study, we evaluated the in vitro antiviral efficacy of emetine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and found it to be a low nanomolar (nM) inhibitor. Read More

Antiviral Res 2021 May 8;189:105059. Epub 2021 Mar 8.

School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA; Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA. Electronic address:

Filoviruses, mainly consisting of Ebola viruses (EBOV) and Marburg viruses (MARV), are enveloped negative-strand RNA viruses which can infect humans to cause severe hemorrhagic fevers and outbreaks with high mortality rates. The filovirus infection is mediated by the interaction of viral envelope glycoprotein (GP) and the human endosomal receptor Niemann-Pick C1 (NPC1). Blocking this interaction will prevent the infection. Read More

Antiviral Res 2021 May 9;189:105061. Epub 2021 Mar 9.

Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. Electronic address:

Coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV) may result in severe liver disease and frequent progression to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that HBV replication is suppressed by replicating HCV and often rebounds after treatment with drugs against HCV. Thus, a highly efficient cell culture system permissive for HBV/HCV would facilitate investigation on the interaction and pathogenesis after coinfection. Read More

Antiviral Res 2021 Apr 22;188:105022. Epub 2021 Feb 22.

Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address:

Antiviral Res 2021 Apr 12;188:105046. Epub 2021 Feb 12.

Research Center in Infectious Diseases, CHU de Québec- Laval University, Quebec City, QC, Canada. Electronic address:

This study aimed at understanding the impact of different substitutions at codon 715 localized in the region II of the palm domain of herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) DNA polymerases (pol). Here, we report a new theoretical mutation V715S that confers resistance of HSV-1 to foscarnet/acyclovir (5.6- and 9. Read More

Antiviral Res 2021 Apr 10;188:105035. Epub 2021 Feb 10.

Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address:

Pimodivir exerts an antiviral effect on the early stages of influenza A virus replication by inhibiting the cap-binding function of polymerase basic protein 2 (PB2). In this study, we used a combination of sequence analysis and phenotypic methods to evaluate pimodivir susceptibility of influenza A viruses collected from humans and other hosts. Screening PB2 sequences for substitutions previously associated with reduced pimodivir susceptibility revealed a very low frequency among seasonal viruses circulating in the U. Read More

Antiviral Res 2021 Apr 9;188:105024. Epub 2021 Feb 9.

Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy. Electronic address:

Background: Human cytomegalovirus (HCMV) remains an important cause of transplant-related morbidity and mortality. The incidence of HCMV recurrence in the donor seronegative (D-)/recipient seropositive (R+) group is significantly higher than in other serostatus combinations as a result of a lack of pre-existing HCMV-specific memory T-lymphocytes in the donor, coupled with the eradication of the recipient's cellular immunity due to the conditioning regimen.

Case Presentation: We describe the case of an 8-year-old βE-thalassemic girl from Bangladesh who was seropositive for human cytomegalovirus (HCMV) and underwent hematopoietic stem cell transplantation from a HLA-matched, unrelated, HCMV-seronegative donor. Read More

Antiviral Res 2021 Apr 10;188:105034. Epub 2021 Feb 10.

Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada; Department of Otolaryngology, Head & Neck Surgery, The University of Western Ontario, London, ON, Canada; Department of Oncology, The University of Western Ontario, London, ON, Canada; London Regional Cancer Program, Lawson Health Research Institute, London, ON, Canada. Electronic address:

Human adenoviruses (HAdV) are ubiquitous human pathogens that cause a significant burden of respiratory, ocular, and gastrointestinal illnesses. Although HAdV infections are generally self-limiting, pediatric and immunocompromised individuals are at particular risk for developing severe disease. Currently, no approved antiviral therapies specific to HAdV exist. Read More

Antiviral Res 2021 Apr 10;188:105036. Epub 2021 Feb 10.

Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata City, Japan; Infectious Diseases Research Center of Niigata University in Myanmar, Yangon, Yangon Region, Myanmar.

Baloxavir marboxil has been used for influenza treatment since March 2018 in Japan. After baloxavir treatment, the most frequently detected substitution is Ile38Thr in polymerase acidic protein (PA/I38T), and this substitution reduces baloxavir susceptibility in influenza A viruses. To rapidly investigate the frequency of PA/I38T in influenza A (H1N1)pdm09 and A (H3N2) viruses in clinical samples, we established a rapid real-time system to detect single nucleotide polymorphisms in PA, using cycling probe real-time PCR. Read More

Antiviral Res 2021 Apr 10;188:105038. Epub 2021 Feb 10.

Division of Biomedical Sciences, Mercer University School of Medicine, Macon, GA, USA. Electronic address:

As the second leading cause of death in the United States, cancer has a considerable impact on society, and one cellular process that is commonly dysregulated in many cancers is the post-translational modification of proteins by the Small Ubiquitin-like Modifier (SUMO; sumoylation). We documented that sumoylation processes are up-regulated in lymphoma tissues in the presence of Latent Membrane Protein-1 (LMP1), the principal oncoprotein of Epstein-Barr virus (EBV). LMP1-mediated dysregulation of cellular sumoylation processes contributes to oncogenesis, modulates innate immune responses, and aids the maintenance of viral latency. Read More

Antiviral Res 2021 04 5;188:105033. Epub 2021 Feb 5.

Gilead Sciences, 333 Lakeside Dr, Foster City, CA, USA.

Remdesivir (RDV) exhibits potent antiviral activity against SARS-CoV-2 and is currently the only drug approved for the treatment of COVID-19. However, little is currently known about the potential for pre-existing resistance to RDV and the possibility of SARS-CoV-2 genetic diversification that might impact RDV efficacy as the virus continue to spread globally. In this study, >90,000 SARS-CoV-2 sequences from globally circulating clinical isolates, including sequences from recently emerged United Kingdom and South Africa variants, and >300 from mink isolates were analyzed for genetic diversity in the RNA replication complex (nsp7, nsp8, nsp10, nsp12, nsp13, and nsp14) with a focus on the RNA-dependent RNA polymerase (nsp12), the molecular target of RDV. Read More

Antiviral Res 2021 03 27;187:105020. Epub 2021 Jan 27.

Aligos Therapeutics, Inc., South San Francisco, USA. Electronic address:

The 3-chymotrypsin-like cysteine protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered a major target for the discovery of direct antiviral agents. We previously reported the evaluation of SARS-CoV-2 3CLpro inhibitors in a novel self-assembled monolayer desorption ionization mass spectrometry (SAMDI-MS) enzymatic assay (Gurard-Levin et al., 2020). Read More

Antiviral Res 2021 03 26;187:105021. Epub 2021 Jan 26.

Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China. Electronic address:

Cathelicidin antimicrobial peptides (human LL-37 and mouse CRAMP) are mainly virucidal to enveloped virus. However, the effects and relative mechanisms of LL-37 and CRAMP on non-enveloped virus are elusive. We herein found that CRAMP expression was significantly up-regulated post non-enveloped Enterovirus 71 (EV71) infection in different tissues of newborn ICR mice, while EV71 replication gradually declined post CRAMP up-regulation, indicating the antiviral potential of cathelicidin against EV71. Read More