antiviral therapeutics / Cyclica, Chinese Academy of Medical Sciences - LARVOL DELTA

Cryo-EM reveals a double oligomeric ring scaffold of the CHIKV nsP3 peptide in complex with the NTF2L domain of host G3BP1. (PubMed, mBio) - "Furthermore, our data indicate that the nsP3-G3BP1 interaction reduces stress granule formation and antagonizes interferon production. Overall, this study provides new knowledge on CHIKV biology and suggests a potential target for developing antiviral therapeutics."

Journal • Chikungunya • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • G3BP1

CRISPR-Cas: a game-changer in vaccine development and the fight against viral infections. (PubMed, Trends Microbiol) - "It is also invaluable in virology research, diagnostics, and antiviral therapeutics...Furthermore, we discuss the potential of the CRISPR-Cas system as an antiviral strategy for tackling newly emerging and re-emerging viruses. Finally, we discuss the potential of CRISPR-Cas-based gene editing for the development of innovative viral vaccines."

Journal • Review • Infectious Disease

Classical swine fever virus recruits ALIX and ESCRT-III to facilitate viral budding. (PubMed, mBio) - "Our findings offer the first comprehensive elucidation of the CSFV budding process and contribute to the identification of antiviral targets, thereby advancing the development of antiviral therapeutics.IMPORTANCEThe endosomal sorting complex required for transport (ESCRT) machinery plays a pivotal role in the sorting of membrane proteins in eukaryotic cells and regulating various stages of infection for numerous viruses...Subsequently, virions are propelled by the kinesin Kif4A along microtubules for egress into the extracellular space. In summary, these findings significantly advance our understanding of CSFV pathogenesis and offer valuable insights into the vesicular transport and budding mechanisms of CSFV particles."

Journal • Infectious Disease • KIF4A

PLSCR1 suppresses SARS-CoV-2 infection by downregulating cell surface ACE2. (PubMed, J Virol) - "These data provide new insights into the interplay between host innate antiviral immunity and SARS-CoV-2 and shed light on novel antiviral therapeutics...In this study, we demonstrated that PLSCR1 inhibited SARS-CoV-2 entry by downregulating the plasma membrane expression of ACE2, the primary receptor for viral entry. Our findings elucidate a novel host-pathogen interaction that not only deepens our understanding of the innate immune response to SARS-CoV-2 but offers potential strategies for therapeutic interventions against COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • ACE2 • IFIH1 • LY6E

Structural insights into Semiliki forest virus receptor binding modes indicate novel mechanism of virus endocytosis. (PubMed, PLoS Pathog) - "Furthermore, the multiple cryo-electron microscopy structures of VLDLR-SFV complexes and mutagenesis studies have demonstrated that under physiological conditions, VLDLR primarily binds to E1-DIII of site-1, site-2, and site-1' at the twofold symmetry axes of SFV virion through LA2, LA3, and LA5, respectively. These findings unveil a novel mechanism for viral entry mediated by receptors, suggesting that conformational transitions in VLDLR induced by multivalent binding of LAs facilitate cellular internalization of SFV, with significant implications for the design of antiviral therapeutics."

Journal • Dyslipidemia

Current antiviral agents against human adenoviruses associated with respiratory infections. (PubMed, Front Pediatr) - "Currently, there are no approved effective and safe antiviral therapeutics for the clinical treatment of HAdV infections, even those that have undergone preclinical/clinical trials. However, many compounds and molecules with anti-HAdV activity have been explored, and some candidates are undergoing clinical development. Here, we reviewed the reported in vitro and in vivo efficacies, as well as the therapeutic potential of these antiviral compounds, providing an overview and a summary of the current status of anti-HAdV drug development."

Journal • Review • Infectious Disease • Respiratory Diseases

Tapered chiral nanoparticles as broad-spectrum thermally stable antivirals for SARS-CoV-2 variants. (PubMed, Proc Natl Acad Sci U S A) - "The incessant mutations of viruses, variable immune responses, and likely emergence of new viral threats necessitate multiple approaches to novel antiviral therapeutics...Considering rapid response to outbreaks, exposure to elevated temperatures causes no change in the antiviral activity of NPs while antibodies are completely deactivated. Testing in mice indicates that the chirality-optimized NPs can serve as thermally stable analogs of antiviral biologics complementing the current spectrum of treatments."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Susceptibility and Resistance of SARS-CoV-2 Variants to LCB1 and Its Multivalent Derivatives. (PubMed, Viruses) - "Importantly, our findings revealed a notable decrease in the blocking capacity of the multivalent LCB1 inhibitor on the interaction between the virus's RBD/S and the cell receptor ACE2 when confronted with the XBB variant compared to WT and the Omicron BA.1 variant. In conclusion, our studies provide valuable insights into the antiviral profiling of multivalent LCB1 inhibitors and offer a promising avenue for the development of novel broad-spectrum antiviral therapeutics."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Host factor MxA restricts Dabie bandavirus infection by targeting the viral NP protein to inhibit NP-RdRp interaction and ribonucleoprotein activity. (PubMed, J Virol) - "Uncovering the mechanisms of DBV-host interactions is necessary to understand the viral pathogenesis and host response and may advance the development of antiviral therapeutics...Consistently, they were then shown to be important for MxA targeting of NP and obstruction of the NP-RdRp association. These findings unravel the restrictive role of MxA in DBV infection and the underlying mechanism, expanding our knowledge of the virus-host interactions."

Journal • Infectious Disease

Virus-induced lncRNA-BTX allows viral replication by regulating intracellular translocation of DHX9 and ILF3 to induce innate escape. (PubMed, Cell Rep) - "Put simply, lncRNA-BTX facilitates DHX9's return to the cytoplasm and retains ILF3 within the nucleus, promoting viral replication. This work unveils a strategy developed by the virus to bypass host innate immunity, thus providing a potential target for antiviral therapeutics."

Journal • Infectious Disease

A First-In-Human Phase 1 Study of Simnotrelvir, a 3CL-like Protease Inhibitor for Treatment of COVID-19, in Healthy Adult Subjects. (PubMed, Eur J Pharm Sci) - P1 | "Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90% inhibition of SARS-CoV-2 in vitro at 750mg/100mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen."

Journal • P1 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Current understanding of nucleoside analogs inhibiting the SARS-CoV-2 RNA-dependent RNA polymerase. (PubMed, Comput Struct Biotechnol J) - "Since the outbreak of the COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) has become a main target for antiviral therapeutics due to its essential role in viral replication and transcription...This review summarizes previous experimental findings and mechanistic investigations of nucleoside analogs inhibiting SARS-CoV-2 RdRp. It would guide the rational design of antiviral medications and research into viral transcriptional mechanisms."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

SARS-CoV-2 induces cardiomyocyte apoptosis and inflammation but can be ameliorated by ACE inhibitor Captopril. (PubMed, Antiviral Res) - "Furthermore, we found that Captopril (hypotensive drugs targeting ACE) treatment could alleviate SARS-CoV-2 induced inflammatory response and apoptosis in cardiomyocytes via inactivating TNF signaling pathways, suggesting Captopril may be beneficial for reducing COVID-19 associated cardiomyopathy. These findings preliminarily explain the molecular mechanism of pathological cardiac injury caused by SARS-CoV-2 infection, providing new perspectives for the discovery of antiviral therapeutics."

Journal • Cardiomyopathy • Cardiovascular • Fibrosis • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

CRISPR-Cas13d effectively targets SARS-CoV-2 variants, including Delta and Omicron, and inhibits viral infection. (PubMed, MedComm (2020)) - "The recent pandemic of variants of concern (VOC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need for innovative anti-SARS-CoV-2 approaches in addition to vaccines and antiviral therapeutics...The reprogrammed Cas13d exhibited high specificity, efficiency, and rapid deployment properties; therefore, it is promising for antiviral drug development. This system could possibly be used to protect against unexpected SARS-CoV-2 variants carrying multiple mutations."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Extracellular vesicles mediate antibody-resistant transmission of SARS-CoV-2. (PubMed, Cell Discov) - "Consistently, the constructed 3D images show that intact EVs could be taken up by recipient cells directly, supporting vesicle-mediated cell-to-cell transmission of SARS-CoV-2. Our findings reveal a novel mechanism of receptor-independent SARS-CoV-2 infection via cell-to-cell transmission, provide new insights into antibody resistance of SARS-CoV-2 and suggest potential targets for future antiviral therapeutics."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Transcriptome profiling highlights regulated biological processes and type III interferon antiviral responses upon Crimean-Congo hemorrhagic fever virus infection. (PubMed, Virol Sin) - "Furthermore, we demonstrate that not only type I but also type III IFNs (even at low dosages) have substantial anti-CCHFV activities. Collectively, the data may provide new and comprehensive insights into the virus-host interactions and particularly highlights the potential role of type III IFNs in restricting CCHFV, which may help inform further mechanistic delineation of the viral infection and development of anti-CCHFV strategies."

Journal • Hematological Disorders • Infectious Disease

Crystal structure of the Rubella virus protease reveals a unique papain-like protease fold. (PubMed, J Biol Chem) - "We also demonstrate that RubPro possesses deubiquitylation activity, suggesting a potential role of RubPro in modulating the host's innate immune responses. We anticipate these structural and functional insights of RubPro will advance our current understanding of its function and help facilitate more structure-based research into the RUBV replication machinery, in hopes of developing antiviral therapeutics against RUBV."

Journal • Dermatology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The long non-coding RNA LNC_000397 negatively regulates PRRSV replication through induction of interferon-stimulated genes. (PubMed, Virol J) - "LNC_000397 negatively regulated PRRSV replication by inducing interferon-stimulated genes (ISGs) expression. Our study is the first report unveiling the role of host lncRNA in regulating PRRSV replication, which might be beneficial for the development of novel antiviral therapeutics."

Journal • Herpes Simplex • Infectious Disease • Respiratory Diseases • Targeted Protein Degradation • MX1

Gasdermin D Inhibits Coronavirus Infection by Promoting the Noncanonical Secretion of Beta Interferon. (PubMed, mBio) - "These findings showed that GSDMD dampens coronavirus infection by an uncovered GSDMD-mediated IFN secretion, which may present a novel target of coronavirus antiviral therapeutics...We here show that alphacoronavirus TGEV triggered pyroptosis and upregulated GSDMD expression, while GSDMD broadly suppressed the infection of enteric coronavirus TGEV and PDCoV by its pore-forming activity via promoting unconventional release of IFN-β. Our study highlights the importance of GSDMD as a regulator of innate immunity and may open new avenues for treating coronavirus infection."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Oncology • Respiratory Diseases • IFNB1 • KEAP1

Antiviral Effect of Ginsenoside Rb2 and Rb3 Against Bovine Viral Diarrhea Virus and Classical Swine Fever Virus in vitro. (PubMed, Front Vet Sci) - "Currently, no effective antiviral therapeutics are available to control their infection...In addition, our results suggest that the possible antiviral mechanism of Rb2 might be related to its ability to affect the translation of these viruses. Obtained results suggest that ginsenoside Rb2 and Rb3 have a potential for effective treatment against Pestivirus infection."

Journal • Preclinical • Infectious Disease

2-((1H-indol-3-yl)thio)-N-phenyl-acetamides: SARS-CoV-2 RNA-dependent RNA polymerase inhibitors. (PubMed, Antiviral Res) - "Despite intensive and global efforts to discover and develop novel antiviral therapies, only Remdesivir has been approved as a treatment for COVID-19. Therefore, effective antiviral therapeutics are still urgently needed to combat and halt the pandemic...However, higher concentrations of these compounds are needed to effectively block HCoV-NL63 replication. Together, our findings successfully identified 4-46b and 6-72-2a as promising inhibitors against SARS-CoV-2 RdRp."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Icariin, Formononetin and Caffeic Acid Phenethyl Ester Inhibit Feline Calicivirus Replication In Vitro. (PubMed, Arch Virol) - "Antiviral therapy is one of the most effective ways to control FCV infection...Finally, we found that ICA has an antagonistic effect on FMN and CAPE in FCV infection, and FMN has a synergistic effect with CAPE against FCV infection. Our results showed that ICA, FMN and CAPE may be potential drug candidates for FCV-induced diseases."

Journal • Preclinical • Immunology • Infectious Disease • Inflammation

The Analysis of Dynamic Changes and Prognosis of Posner-Schlossman Syndrome with Cytomegalovirus Infection and Antiviral Therapy. (PubMed, J Ophthalmol) - "To analyze how keratic precipitate (KP) morphology changes during Posner-Schlossman syndrome (PSS) prognosis and raise medication suggestions on 2% ganciclovir eye drops. Paired aqueous humor and serum CMV IgG tests were recommended in PSS patients with coin-shaped KPs. 2% ganciclovir eye drops improved prognosis; and steroids dosage reduced significantly."

Journal • Cytomegalovirus Infection • Infectious Disease

Rice stripe virus: Exploring Molecular Weapons in the Arsenal of a Negative-Sense RNA Virus. (PubMed, Annu Rev Phytopathol) - "Understanding these issues will facilitate the design of novel antiviral therapies for management and contribute to a more detailed understanding of negative-sense virus-host interactions at the molecular level. Expected final online publication date for the Annual Review of Phytopathology, Volume 59 is August 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates."

Journal • Infectious Disease • Respiratory Diseases

H1N1 exposure during the convalescent stage of SARS-CoV-2 infection results in enhanced lung pathologic damage in hACE2 transgenic mice. (PubMed, Emerg Microbes Infect) - "Moreover, upon H1N1 exposure on 7 and 14 dpi of SARS-CoV-2 infection, the lymphocyte population activated at a lower level with T cell suppressed in both PBMC and lung. These findings will be valuable for evaluating antiviral therapeutics and vaccines as well as guiding public health work."

Journal • Preclinical • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases