Favipiravir, umifenovir and camostat mesylate: a comparative study against SARS-CoV-2

Since the first cases the coronavirus disease caused by SARS-CoV-2 (COVID-19) reported in December 2019, worldwide continuous efforts have been placed both for the prevention and treatment of this infectious disease. As new variants of the virus emerge, the need for an effective antiviral treatment continues. The concept of preventing SARS-CoV-2 on both pre-entry and post-entry stages has not been much studied. Therefore, we compared the antiviral activities of three antiviral drugs which have been currently used in the clinic. In silico docking analyses and in vitro viral infection in Vero E6 cells were performed to delineate their antiviral effectivity when used alone or in combination. Both in silico and in vitro results suggest that the combinatorial treatment by favipiravir and umifenovir or camostat mesylate has more antiviral activity against SARS-CoV-2 rather than single drug treatment. These results suggest that inhibiting both viral entry and viral replication at the same time is much more effective for the antiviral treatment of SARS-CoV-2.

Rapid Antigen Test Combine with Nucleic Acid Detection: A Better Strategy for COVID-19 Screening at Points of Entry

The coronavirus disease 2019 (COVID-19) pandemic has imposed an enormous disease burden worldwide, and the Delta variant now has become dominant in 53 countries. Recently published studies have shown that during periods of high viral load, rapid antigen tests (RAT) yield similar results to reverse transcriptase-polymerase chain reaction (RT-PCR) tests, and when used in serial screening (e.g., every three days), it has a high sensitivity. In this perspective, we recommend RT-PCR combined with RAT at points of entry: (i) RAT can be added to the detection phase at ports of entry to detect asymptomatic infections as early as possible; (ii) RAT can be added to post-entry quarantine every three days or less to reduce the rate of missed detection in later quarantine; (iii) Adding regular RAT to regular PCR testing for key airport personnel to prevent cross-infection and conduct closed-off management. In the face of sporadic Delta variant outbreaks, the combination of the two could help rapid triage and management of suspected populations at an early stage and thus contain the outbreak more quickly and effectively. We also discuss the issue whether the current antigen detection reagents can cope with various SARS-CoV-2 variants.

Replication is the key barrier during the dual-host adaption of mosquito-borne flaviviruses

Mosquito-borne flaviviruses (MBFs) adapt to a dual-host transmission circle between mosquitoes and vertebrates. Dual-host affiliated insect-specific flaviviruses (dISFs), discovered from mosquitoes, are phylogenetically similar to MBFs but do not infect vertebrates. Thus, dISF-MBF chimeras could be an ideal model to study the dual-host adaption of MBFs. Using the pseudo-infectious reporter virus particle and reverse genetics systems, we found dISFs entered vertebrate cells as efficiently as the MBFs, but failed to initiate replication. Exchange of the un-translational regions (UTRs) of Donggang virus (DONV), an dISF, with those from Zika virus (ZIKV) rescued DONV replication in vertebrate cells and critical secondary RNA structures were further mapped. Essential UTR-binding host factors were screened for ZIKV replication in vertebrate cells, displaying different binding patterns. Therefore, our data demonstrate a post-entry cross-species transmission mechanism of MBFs, while UTR-host interaction is critical for dual-host adaption.

Superinfection Exclusion of Alphaherpesviruses Interferes with Virion Trafficking

Superinfection exclusion (SIE) is a phenomenon in which a primary viral infection interferes with secondary viral infections within that same cell. Although SIE has been observed across many viruses, it has remained relatively understudied. A recently characterized glycoprotein D (gD) -independent SIE of alphaherpesviruses presents a novel mechanism of co-infection restriction for Herpes Simplex Virus Type 1 (HSV-1) and Pseudorabies virus (PRV). In this study, we evaluated the role of multiplicity of infection (MOI), receptor expression, and trafficking of virions to gain greater insight into potential mechanisms of alphaherpesvirus SIE. We observed that high MOI secondary viral infections were able to overcome SIE in a manner that was independent of receptor availability. Utilizing recombinant viruses expressing fluorescent protein fusions, we assessed virion localization during SIE through live fluorescent microscopy of dual-labeled virions and localization of capsid assemblies. Analysis of these assemblies confirmed changes in the distribution of capsids during SIE. These results indicate that SIE during PRV infection inhibits viral entry or fusion while HSV-1 SIE inhibits infection through a post-entry mechanism. Although the timing and phenotype of SIE is similar between alphaherpesviruses, the related viruses implement different mechanisms to restrict coinfection.

Complete Genome Sequence of Vallota Mosaic Virus Detected In A Narcissus Bulb Imported From The United States to Japan

Narcissus (Narcissus albidus) imported from the United States exhibited leaf chlorosis during post-entry quarantine. We employed next-generation sequencing (NGS) on symptomatic leaf samples and detected vallota mosaic virus (ValMV) belonging to the genus Potyvirus, family Potyviridae, as the viral agent. Sanger sequencing of PCR and rapid amplification of cDNA ends based on NGS contigs revealed that ValMV was 9,451 nucleotides (nt) in length, excluding the poly(A) tail. Nucleotide and amino acid (aa) sequences of the coat protein region had over 98% identity to previously reported ValMV isolates. At each of the 10 mature protein regions, however, sequence identity with other potyviruses was 49.5–71.9% nt and 18.3–78.9% aa, values that are below the species demarcation criteria for Potyviridae. Phylogenetic analysis revealed that our ValMV isolate is most closely related to known ValMV and is grouped within other potyviruses. Taken together, our results indicate that the newly isolated ValMV belongs to a distinct species of Potyvirus. This study provides the first report of the complete ValMV genome sequence and the first record of this virus from the narcissus.

Complete Genome Sequence of a Novel Potyvirus Infecting Miscanthus Sinensis (Silver Grass)

Here, we describe the full-length genome sequence of a novel potyvirus, tentatively named “miscanthus sinensis mosaic virus” (MsiMV), isolated from Miscanthus sinensis (silver grass) held in a post entry quarantine facility following its initial import into Western Australia, Australia. The MsiMV genome encompasses 9604 nucleotides (nt) encoding a 3071 amino acids (aa) polyprotein with conserved sequence motifs. The MsiMV genome is most closely related to sorghum mosaic virus (SrMV) with 74% nt and 78.5% aa sequence identity to the SrMV polyprotein region. Phylogenetic analysis based on the polyprotein grouped MsiMV with SrMV, sugarcane mosaic virus (SCMV) and maize dwarf mosaic virus (MDMV). This is the first report of a novel monopartite ssRNA virus in Miscanthus sinensis related to members of the genus Potyvirus in the family Potyviridae.