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Journal Club by RdRp Summit The Journal Club will begin in September and is planned to take place on the first Thursday of each month. We are now collecting nominations for potential speakers. Please...

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Highly ordered viral proteins like SARS CoV2 RNA-dependent RNA polymerase (RdRp) can evade CD8+ T cell recognition by limiting antigen processing. Increasing protein intrinsic disorder, by dividing Rd...

Highly ordered viral proteins like SARS CoV2 RNA-dependent RNA polymerase (RdRp) can evade CD8+ T cell recognition by limiting antigen processing. Increasing protein intrinsic disorder, by dividing Rd...

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Ambiviruses are fungal-infecting circular RNA viruses that uniquely combine viroid-like and viral features, yet the function of their conserved ORF-B protein and their effects on hosts remain unknown,...

GTSF1 is an essential activating cofactor for PIWI proteins in many metazoans. In the nematode Caenorhabditis elegans, however, GTSF-1 does not bind PIWI, but is associated with the RNA-dependent RNA ...

The COVID-19 pandemic caused by SARS-CoV-2 has resulted in millions of deaths worldwide. Despite the emergence of antiviral drugs and vaccines targeting 3CLpro and RNA-dependent RNA polymerase (Rdrp), the virus’s continuous mutation underscores the need for novel therapeutic approaches that target highly conserved viral regions. PLpro is an attractive target due to its roles in viral replication and host immune regulation. However, research on nanobodies targeting PLpro remains in its infancy. This study provides significant insights into the antiviral and anti-inflammatory functions of two nanobodies, NbP1 and NbP2, which specifically disrupt the PLpro/ISG15 interaction interface. Our findings have important implications for drug development targeting SARS-CoV-2, highlighting the potential of nanobody-based therapeutics to simultaneously inhibit viral replication and suppress pathological inflammation.

Background SARS-CoV-2 remains a global health threat because ongoing viral evolution and immune evasion reduce the effectiveness of existing therapies. SNS812 is an inhaled small interfering RNA targe...

by Xingyang Cui, Hao Song, Xinyi Huang, Dasong Xia, Yongbo Yang, Xiaoxiao Tian, Tao Wang, Guoqing Liu, Zameel Saleem, Haiwei Wang, Tongqing An Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant diseases, causing tremendous economic losses to the global swine industry. Accumulating evidence indicates that recombination between PRRSV-2 strains, particularly those involving NADC30-like PRRSV-2 variants, has been responsible for outbreaks across several countries. However, the key proteins or amino acids associated with PRRSV-2 recombination remain unclear. In this study, two representative PRRSV-2 strains (the NADC30-like HeB108 strain from lineage 1 and the HP-PRRSV HuN4 strain from lineage 8) were serially passaged in the presence of ribavirin. Amino acid substitutions associated with ribavirin resistance were identified in the RNA-dependent RNA polymerase (RdRp) and helicase of the passaged viruses. Using the infectious clones PRRSV-2 HeB108 and HuN4, ribavirin-resistant mutants with single or multiple amino acid substitutions were generated. Notably, the mutants HeB108-VGSS and HuN4-TNII, with multiple amino acid substitutions, showed higher fidelity and lower pathogenicity in infected piglets than their parental viruses. Furthermore, the potential decreased recombination risk correlated with increased polymerase fidelity. In an inter-lineage co-infection assay on primary alveolar macrophages, the I360V substitution in RdRp reduced the recombination frequency of NADC30-like PRRSV-2 HeB108 as determined by both Sanger sequencing and nanopore long-read RNA sequencing. The results identified a key amino acid associated with viral recombination in NADC30-like PRRSV-2 and provide an editing target for developing safer vaccines that are less prone to recombination.

by Xingyang Cui, Hao Song, Xinyi Huang, Dasong Xia, Yongbo Yang, Xiaoxiao Tian, Tao Wang, Guoqing Liu, Zameel Saleem, Haiwei Wang, Tongqing An Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant diseases, causing tremendous economic losses to the global swine industry. Accumulating evidence indicates that recombination between PRRSV-2 strains, particularly those involving NADC30-like PRRSV-2 variants, has been responsible for outbreaks across several countries. However, the key proteins or amino acids associated with PRRSV-2 recombination remain unclear. In this study, two representative PRRSV-2 strains (the NADC30-like HeB108 strain from lineage 1 and the HP-PRRSV HuN4 strain from lineage 8) were serially passaged in the presence of ribavirin. Amino acid substitutions associated with ribavirin resistance were identified in the RNA-dependent RNA polymerase (RdRp) and helicase of the passaged viruses. Using the infectious clones PRRSV-2 HeB108 and HuN4, ribavirin-resistant mutants with single or multiple amino acid substitutions were generated. Notably, the mutants HeB108-VGSS and HuN4-TNII, with multiple amino acid substitutions, showed higher fidelity and lower pathogenicity in infected piglets than their parental viruses. Furthermore, the potential decreased recombination risk correlated with increased polymerase fidelity. In an inter-lineage co-infection assay on primary alveolar macrophages, the I360V substitution in RdRp reduced the recombination frequency of NADC30-like PRRSV-2 HeB108 as determined by both Sanger sequencing and nanopore long-read RNA sequencing. The results identified a key amino acid associated with viral recombination in NADC30-like PRRSV-2 and provide an editing target for developing safer vaccines that are less prone to recombination.