scholarly journals The Antiviral Effect of the Chemical Compounds Targeting DED/EDh Motifs of the Viral Proteins on Lymphocytic Choriomeningitis Virus and SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1220
Author(s):  
Mya Myat Ngwe Tun ◽  
Kouichi Morita ◽  
Takeshi Ishikawa ◽  
Shuzo Urata
Keyword(s):  
Drug Target ◽  
Docking Simulation ◽  
Chemical Compounds ◽  
Viral Proteins ◽  
Antiviral Effect ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Lassa Virus ◽  
Common Motif ◽  
Post Entry

Arenaviruses and coronaviruses include several human pathogenic viruses, such as Lassa virus, Lymphocytic choriomeningitis virus (LCMV), SARS-CoV, MERS-CoV, and SARS-CoV-2. Although these viruses belong to different virus families, they possess a common motif, the DED/EDh motif, known as an exonuclease (ExoN) motif. In this study, proof-of-concept studies, in which the DED/EDh motif in these viral proteins, NP for arenaviruses, and nsp14 for coronaviruses, could be a drug target, were performed. Docking simulation studies between two structurally different chemical compounds, ATA and PV6R, and the DED/EDh motifs in these viral proteins indicated that these compounds target DED/EDh motifs. The concentration which exhibited modest cell toxicity was used with these compounds to treat LCMV and SARS-CoV-2 infections in two different cell lines, A549 and Vero 76 cells. Both ATA and PV6R inhibited the post-entry step of LCMV and SARS-CoV-2 infection. These studies strongly suggest that DED/EDh motifs in these viral proteins could be a drug target to combat two distinct viral families, arenaviruses and coronaviruses.

Antiviral Effect of Interferon Lambda Against Lymphocytic Choriomeningitis Virus

2015 ◽  
Vol 35 (7) ◽  
pp. 540-553 ◽  
Author(s):  
Lubomira Lukacikova ◽  
Ingrid Oveckova ◽  
Tatiana Betakova ◽  
Katarina Laposova ◽  
Katarina Polcicova ◽  
...  
Keyword(s):  
Antiviral Effect ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Interferon Lambda

scholarly journals Broad-Spectrum Antiviral Activity of Small Interfering RNA Targeting the Conserved RNA Termini of Lassa Virus

2007 ◽  
Vol 51 (6) ◽  
pp. 2215-2218 ◽  
Author(s):  
Stefanie Müller ◽  
Stephan Günther
Keyword(s):  
Gene Expression ◽  
Small Interfering Rna ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Lassa Virus ◽  
Small Interfering Rnas ◽  
Rna Targeting ◽  
Expression Construct ◽  
Interfering Rna ◽  
Virus Strains

ABSTRACT Small interfering RNAs targeting the conserved RNA termini upstream of NP and L gene were found to reduce reporter gene expression from Lassa virus replicon and Lassa virus mRNA expression construct and to inhibit replication of different Lassa virus strains, lymphocytic choriomeningitis virus, and Mopeia virus in cell culture.

scholarly journals Evolution of Recombinant Lymphocytic Choriomeningitis Virus/Lassa Virus In Vivo Highlights the Importance of the GPC Cytosolic Tail in Viral Fitness

2014 ◽  
Vol 88 (15) ◽  
pp. 8340-8348 ◽  
Author(s):  
R. Sommerstein ◽  
J. Ramos da Palma ◽  
S. Olschlager ◽  
A. Bergthaler ◽  
L. Barba ◽  
...  
Keyword(s):  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Viral Fitness ◽  
Lassa Virus

scholarly journals Viral proteins and RNAs in BHK cells persistently infected by lymphocytic choriomeningitis virus.

1983 ◽  
Vol 48 (1) ◽  
pp. 262-270 ◽  
Author(s):  
B A van der Zeijst ◽  
N Bleumink ◽  
L V Crawford ◽  
E A Swyryd ◽  
G R Stark
Keyword(s):  
Viral Proteins ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Persistently Infected ◽  
Bhk Cells

scholarly journals A Highly Conserved Leucine in Mammarenavirus Matrix Z Protein Is Required for Z Interaction with the Virus L Polymerase and Z Stability in Cells Harboring an Active Viral Ribonucleoprotein

2018 ◽  
Vol 92 (11) ◽  
Author(s):  
Masaharu Iwasaki ◽  
Juan C. de la Torre
Keyword(s):  
Hemorrhagic Fever ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Negative Regulator ◽  
Lassa Virus ◽  
Membrane Composition ◽  
Subcellular Compartment ◽  
Rapid Degradation ◽  
Wide Range ◽  
Z Protein

ABSTRACT Mammarenaviruses cause chronic infections in their natural rodent hosts. Infected rodents shed infectious virus into excreta. Humans are infected through mucosal exposure to aerosols or direct contact of abraded skin with fomites, resulting in a wide range of manifestations from asymptomatic or mild febrile illness to severe life-threatening hemorrhagic fever. The mammarenavirus matrix Z protein has been shown to be a main driving force of virus budding and to act as a negative regulator of viral RNA synthesis. To gain a better understanding of how the Z protein exerts its several different functions, we investigated the interaction between Z and viral polymerase L protein using the prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV). We found that in the presence of an active viral ribonucleoprotein (vRNP), the Z protein translocated from nonionic detergent-resistant, membrane-rich structures to a subcellular compartment with a different membrane composition susceptible to disruption by nonionic detergents. Alanine (A) substitution of a highly conserved leucine (L) at position 72 in LCMV Z protein abrogated Z-L interaction. The L72A mutation did not affect the stability or budding activity of Z when expressed alone, but in the presence of an active vRNP, mutation L72A promoted rapid degradation of Z via a proteasome- and lysosome-independent pathway. Accordingly, L72A mutation in the Z protein resulted in nonviable LCMV. Our findings have uncovered novel aspects of the dynamics of the Z protein for which a highly conserved L residue was strictly required. IMPORTANCE Several mammarenaviruses, chiefly Lassa virus (LASV), cause hemorrhagic fever disease in humans and pose important public health concerns in their regions of endemicity. Moreover, mounting evidence indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. The mammarenavirus matrix Z protein plays critical roles in different steps of the viral life cycle by interacting with viral and host cellular components. Here we report that alanine substitution of a highly conserved leucine residue, located at position 72 in LCMV Z protein, abrogated Z-L interaction. The L72A mutation did not affect Z budding activity but promoted its rapid degradation in the presence of an active viral ribonucleoprotein (vRNP). Our findings have uncovered novel aspects of the dynamics of the Z protein for which a highly conserved L residue was strictly required.

scholarly journals Identification of the Lymphocytic Choriomeningitis Virus (LCMV) Proteins Required To Rescue LCMV RNA Analogs into LCMV-Like Particles

2002 ◽  
Vol 76 (12) ◽  
pp. 6393-6397 ◽  
Author(s):  
Ki Jeong Lee ◽  
Mar Perez ◽  
Daniel D. Pinschewer ◽  
Juan Carlos de la Torre
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Neutralizing Antibodies ◽  
Rna Replication ◽  
Viral Proteins ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Reverse Genetic ◽  
Transfected Cells ◽  
Reverse Genetic Approach

ABSTRACT We have used a reverse genetic approach to identify the viral proteins required for packaging and assembly of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). Plasmids encoding individual LCMV proteins under the control of an RNA polymerase II promoter were cotransfected with a plasmid containing an LCMV minigenome (MG). Intracellular synthesis of the LCMV MG was driven by T7 RNA polymerase whose expression was also mediated by a Pol II promoter. The supernatant from transfected cells was passaged onto fresh cells that were subsequently infected with LCMV to provide the minimal viral trans-acting factors, NP and L, that are required for LCMV MG RNA replication and expression. Reconstitution of LCMV-specific packaging and passage was detected by expression of the chloramphenicol acetyl transferase (CAT) reporter gene present in the MG. NP and L did not direct detectable levels of MG passage. Addition of Z and GP resulted in high levels of passage of CAT activity, which could be prevented by LCMV neutralizing antibodies. Passage of LCMV MG was inhibited by omission of either GP or Z.

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