Sanjay Barua - Academia.edu (original) (raw)
Papers by Sanjay Barua
Journal of Immunology and Immunopathology, 2004
The hexon gene sequence of fowl adenovirus 4 of Indian origin was analysed along with other fowl ... more The hexon gene sequence of fowl adenovirus 4 of Indian origin was analysed along with other fowl adenoviruses. The neighbour joining tree of the 12 serotypes of group I FAVs at the N-terminus of hexon gene revealed a close genetic relationship between FAV4 and FAV9 while the complete hexon gene tree revealed that FAV4 was related to FAV10. These facts indicate that FAV4 might have evolved by a recombination of FAV9 and FAV10.
Journal of Immunology and Immunopathology, 2004
The restriction enzyme analysis of fowl adenovirus 4 DNA was carried out with the enzymes Xbal, B... more The restriction enzyme analysis of fowl adenovirus 4 DNA was carried out with the enzymes Xbal, BamHI, Dral, EcoRI, Hindlll, Bgl ll, Pstl, Smal, Notl, Ndel and Sacl in order to ascertain the restriction profile. The restriction profile of FAV4 DNA (Indian isolate) was similar to the restriction profile of FAV4 reference strain KR-5. The total genomic size of FAV4 DNA was estimated to be 46 kb. Comparison of restriction profile of FAV4 (Indian isolate) with that of FAV10 revealed considerable variation with the enzymes BamHI, Bglll, Dral and Smal. The study revealed that restriction enzyme analysis could be a good basis for differentiation of FAV strains.
Virusdisease, Jul 17, 2015
Camelpox virus (CMLV), a close variant of variola virus (VARV) infects camels worldwide. The zoon... more Camelpox virus (CMLV), a close variant of variola virus (VARV) infects camels worldwide. The zoonotic infections reported from India signify the need to study the host-range genes-responsible for host tropism. We report sequence and phylogenetic analysis of five hostrange genes: cytokine response modifier B (crmB), chemokine binding protein (ckbp), viral schlafen-like (v-slfn), myxomavirus T4-like (M-T4-like) and b5r of CMLVs isolated from outbreaks in India. Comparative analysis revealed that these genes are conserved among CMLVs and shared 94.5-100 % identity at both nucleotide (nt) and amino acid (aa) levels. All genes showed identity (59.3-98.4 %) with cowpox virus (CPXV) while three genes-crmB, ckbp and b5r showed similarity (92-96.5 %) with VARVs at both nt and aa levels. Interestingly, three consecutive serine residue insertions were observed in CKBP protein of CMLV-Delhi09 isolate which was similar to CPXV-BR and VACVs, besides five point mutations (K53Q, N67I, F84S, A127T and E182G) were also similar to zoonotic OPXVs. Further, few inconsistent point mutation(s) were also observed in other gene(s) among Indian CMLVs. These indicate that different strains of CMLVs are circulating in India and these mutations could play an important role in adaptation of CMLVs in humans. The phylogeny revealed clustering of all CMLVs together except CMLV-Delhi09 which grouped separately due to the presence of specific point mutations. However, the topology of the concatenated phylogeny showed close evolutionary relationship of CMLV with VARV and TATV followed by CPXV-RatGer09/1 from Germany. The availability of this genetic information will be useful in unveiling new strategies to control emerging zoonotic poxvirus infections.
Virus Research, May 1, 2023
Reviews in Medical Virology, Jan 15, 2021
Mitogen‐activated protein kinases (MAPKs) play a key role in complex cellular processes such as p... more Mitogen‐activated protein kinases (MAPKs) play a key role in complex cellular processes such as proliferation, development, differentiation, transformation and apoptosis. Mammals express at least four distinctly regulated groups of MAPKs which include extracellular signal‐related kinases (ERK)‐1/2, p38 proteins, Jun amino‐terminal kinases (JNK1/2/3) and ERK5. p38 MAPK is activated by a wide range of cellular stresses and modulates activity of several downstream kinases and transcription factors which are involved in regulating cytoskeleton remodeling, cell cycle modulation, inflammation, antiviral response and apoptosis. In viral infections, activation of cell signalling pathways is part of the cellular defense mechanism with the basic aim of inducing an antiviral state. However, viruses can exploit enhanced cell signalling activities to support various stages of their replication cycles. Kinase activity can be inhibited by small molecule chemical inhibitors, so one strategy to develop antiviral drugs is to target these cellular signalling pathways. In this review, we provide an overview on the current understanding of various cellular and viral events regulated by the p38 signalling pathway, with a special emphasis on targeting these events for antiviral drug development which might identify candidates with broad spectrum activity.
Genome Announcements, Aug 28, 2014
The sequencing of the recombinant plasmid containing 2916 bp hexon gene insert of fowl adeno viru... more The sequencing of the recombinant plasmid containing 2916 bp hexon gene insert of fowl adeno virus 4 (FAV4) of Indian origin revealed the complete nucleotide sequence of the FAV4 hexon gene. The sequence analysis revealed an open reading frame of 2814 bp coding for a 937 amino acids long polypeptide with a molecular mass of 106.04 kDa. This sequence was larger than the hexon coding regions of FAV10, HAV40, HAV41, MAV1 and BAV3, while it was smaller than the hexon in HAV2 and HAV5. The Kozak sequence was found at nucleotide position 78, which was similar in FAV10 hexon gene. The codon bias revealed a strong preference for C and to a lesser extent G in the third base position. The splice acceptor sequence in FAV4Ind was located 12 bp upstream of the hexon initiation site of the translation codon, which indicated that FAV4 hexon could be a late gene product. A high degree of amino acid variation (9.6%) was observed between FAV4Ind and FAV10, as compared to the 1.5% variation between FAV4Ind and FAV4KR95. The L1 loop of the hexon gene showed the maximum sequence variation among FAV serotypes, thus it could be used for designing serotype specific PCR primers. The 11 unique amino acid substitutions in FAV4Ind hexon could play a significant role in determining its type specificity.
Indian Journal of Comparative Microbiology, Immunology and Infectious Diseases, 2003
195-202<span style="font-size:9.0pt;mso-ansi-language:EN-IN;mso-bidi-font-weight: bold&qu... more 195-202<span style="font-size:9.0pt;mso-ansi-language:EN-IN;mso-bidi-font-weight: bold">Virulence-associated plasmid (Vap) genes of clinical isolates of Rhodococcus equi were characterized. Isolates were identified by 16S rRNA, choE and <i style="mso-bidi-font-style: normal">traA gene PCR, followed by amplification, cloning and sequencing of 7 Vap<span style="mso-bidi-font-weight: bold"> genes. <span style="font-size:9.0pt;mso-ansi-language:EN-IN;mso-bidi-font-weight: bold">The isolates were found positive for <i style="mso-bidi-font-style: normal">vapA gene family. The comparative sequence analysis of vap genes revealed 99-100% similarity at both nt and aa levels with all sequences. The aa sequences of the predicted Vap proteins<span style="font-size: 9.0pt;mso-ansi-language:EN-IN;mso-bidi-font-weight:bold"> exhibited a high degree of similarity to each other, especially at the carboxy t...
Haryana Veterinarian, 2015
Cases of swinepox were investigated in two piggery units in Sonipat and Rohtak districts of Harya... more Cases of swinepox were investigated in two piggery units in Sonipat and Rohtak districts of Haryana state. Overall morbidity rate, cumulative mortality and case fatality rate due to the disease in both the units were 13.63%, 9.84%, 72.22%, respectively. The disease was characterized by fever, drastic decrease in feed and water intake, dullness, inability to stand and eruptions and scab formation on the skin. Swinepox virus (SWPV) was detected in scabs, spleen and lymph nodes using PCR targeting VLTF-3 gene and sequence analysis. The SWPV from India shared nucleotide identity of 98.9% and aminoacid identity of 96.6% with SWPV from Brazil. Phylogenetic analysis revealed that the SWPV from India was found to cluster closely with SWPV from Brazil with high bootstrap value. Further studies are required on its prevalence in different geographic areas as well as molecular epidemiology.
Genome announcements, Jan 22, 2015
Salmonella enterica subsp. enterica serovar Gallinarum biovar Gallinarum causes fowl typhoid (FT)... more Salmonella enterica subsp. enterica serovar Gallinarum biovar Gallinarum causes fowl typhoid (FT), which results in huge economic losses to poultry farmers in India. We report the draft genome sequence of Salmonella biovar Gallinarum strain VTCCBAA614, isolated from a chicken in an FT affected broiler flock.
Journal of Immunology and Immunopathology, 2005
A recombinant plasmid pcDNA3.1/V5-His-TOPO.fav4hex (8.5 kb) encoding the hexon gene (2916 bp) of ... more A recombinant plasmid pcDNA3.1/V5-His-TOPO.fav4hex (8.5 kb) encoding the hexon gene (2916 bp) of fowl adenovirus 4 was found to express hexon protein in transfected Vero cells as detected by immunoperoxidase test. Vaccination of 3-days old chicken with 50 mg of recombinant plasmid DNA intramuscularly revealed that the vaccinated birds' withstood challenge with 10,000 ID50 of virulent liver passaged FAV4 after 21-days of vaccination while the control (non-vaccinated) birds either died or contracted disease. The field trials of the vaccine exhibited safety and potency. The study reveals that the vaccine could be used as a candidate DNA vaccine to protect the birds against FAV4 infection.
Journal of Immunological Methods
In this study, miRNA profiling of cells infected with lumpy skin disease virus (LSDV) was conduct... more In this study, miRNA profiling of cells infected with lumpy skin disease virus (LSDV) was conducted for the first time. As compared to the mock-infected cells, LSDV-infected primary lamb testicle (LT) cells revealed dysregulation of 64, 85, and 85 miRNAs at 12 hours post-infection (hpi), 48 hpi and 72 hpi, respectively. While some of these miRNAs were found to be specifically dysregulated at a particular time point following LSDV infection, others were commonly dysregulated across all three time points. The analysis of the differentially expressed miRNA-mRNA interaction networks, Gene ontology analysis of the predicted targets and KEGG analysis of the highly enriched pathways revealed several cellular factors/pathways involved in protein/ion/enzyme binding, cell differentiation, movement of subcellular component, calcium reabsorption, aldosterone synthesis and secretion and, melanogenesis. Besides understanding virus replication, virus-host interactions and disease pathogenesis, the...
Scientific Reports
Rho-associated coiled-coil containing protein kinase 1 (ROCK1) intracellular cell signaling pathw... more Rho-associated coiled-coil containing protein kinase 1 (ROCK1) intracellular cell signaling pathway regulates cell morphology, polarity, and cytoskeletal remodeling. We observed the activation of ROCK1/myosin light chain (MLC2) signaling pathway in buffalopox virus (BPXV) infected Vero cells. ROCK1 depletion by siRNA and specific small molecule chemical inhibitors (Thiazovivin and Y27632) resulted in a reduced BPXV replication, as evidenced by reductions in viral mRNA/protein synthesis, genome copy numbers and progeny virus particles. Further, we demonstrated that ROCK1 inhibition promotes deadenylation of viral mRNA (mRNA decay), mediated via inhibiting interaction with PABP [(poly(A)-binding protein] and enhancing the expression of CCR4-NOT (a multi-protein complex that plays an important role in deadenylation of mRNA). In addition, ROCK1/MLC2 mediated cell contraction, and perinuclear accumulation of p-MLC2 was shown to positively correlate with viral mRNA/protein synthesis. Fina...
Molecular Biology and Evolution
Host-dependency factors have increasingly been targeted to minimize antiviral drug resistance. In... more Host-dependency factors have increasingly been targeted to minimize antiviral drug resistance. In this study, we have demonstrated that inhibition of p38 mitogen-activated protein kinase (a cellular protein) suppresses buffalopox virus (BPXV) protein synthesis by targeting p38-MNK1-eIF4E signaling pathway. In order to provide insights into the evolution of drug resistance, we selected resistant mutants by long-term sequential passages (P; n = 60) in the presence of p38 inhibitor (SB239063). The P60-SB239063 virus exhibited significant resistance to SB239063 as compared to the P60-Control virus. To provide mechanistic insights on the acquisition of resistance by BPXV-P60-SB239063, we generated p38-α and p38-ϒ (isoforms of p38) knockout Vero cells by CRISPR/Cas9-mediated genome editing. It was demonstrated that unlike the wild type (WT) virus which is dependent on p38-α isoform, the resistant virus (BPXV-P60-SB239063) switches over to use p38-ϒ so as to efficiently replicate in the ta...
bioRxiv, 2020
Emetine is a FDA-approved drug for the treatment of amebiasis. In the recent times we had also de... more Emetine is a FDA-approved drug for the treatment of amebiasis. In the recent times we had also demonstrated the antiviral efficacy of emetine against some RNA and DNA viruses. Following emergence of the COVID-19, we further evaluated thein vitro antiviral activity of emetine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The therapeutic index of emetine was determined to be 10910.4, at a cytotoxic concentration 50 (CC50) of 1603.8 nM and effective concentration 50 (EC50) of 0.147 nM.Besides, we also demonstrated the protective efficacy of emetine against lethal challenge with infectious bronchitis virus (IBV; a chicken coronavirus) in the embryonated chicken egg infection model. Emetine treatment was shown to decrease viral RNA and protein synthesis without affecting other steps of viral life cycle such as attachment, entry and budding.In a chromatin immunoprecipitation (CHIP) assay, emetine was shown to disrupt the binding of SARS-CoV-2 RNA with eIF4E (eukary...
Journal of Immunology and Immunopathology, 2004
The hexon gene sequence of fowl adenovirus 4 of Indian origin was analysed along with other fowl ... more The hexon gene sequence of fowl adenovirus 4 of Indian origin was analysed along with other fowl adenoviruses. The neighbour joining tree of the 12 serotypes of group I FAVs at the N-terminus of hexon gene revealed a close genetic relationship between FAV4 and FAV9 while the complete hexon gene tree revealed that FAV4 was related to FAV10. These facts indicate that FAV4 might have evolved by a recombination of FAV9 and FAV10.
Journal of Immunology and Immunopathology, 2004
The restriction enzyme analysis of fowl adenovirus 4 DNA was carried out with the enzymes Xbal, B... more The restriction enzyme analysis of fowl adenovirus 4 DNA was carried out with the enzymes Xbal, BamHI, Dral, EcoRI, Hindlll, Bgl ll, Pstl, Smal, Notl, Ndel and Sacl in order to ascertain the restriction profile. The restriction profile of FAV4 DNA (Indian isolate) was similar to the restriction profile of FAV4 reference strain KR-5. The total genomic size of FAV4 DNA was estimated to be 46 kb. Comparison of restriction profile of FAV4 (Indian isolate) with that of FAV10 revealed considerable variation with the enzymes BamHI, Bglll, Dral and Smal. The study revealed that restriction enzyme analysis could be a good basis for differentiation of FAV strains.
Virusdisease, Jul 17, 2015
Camelpox virus (CMLV), a close variant of variola virus (VARV) infects camels worldwide. The zoon... more Camelpox virus (CMLV), a close variant of variola virus (VARV) infects camels worldwide. The zoonotic infections reported from India signify the need to study the host-range genes-responsible for host tropism. We report sequence and phylogenetic analysis of five hostrange genes: cytokine response modifier B (crmB), chemokine binding protein (ckbp), viral schlafen-like (v-slfn), myxomavirus T4-like (M-T4-like) and b5r of CMLVs isolated from outbreaks in India. Comparative analysis revealed that these genes are conserved among CMLVs and shared 94.5-100 % identity at both nucleotide (nt) and amino acid (aa) levels. All genes showed identity (59.3-98.4 %) with cowpox virus (CPXV) while three genes-crmB, ckbp and b5r showed similarity (92-96.5 %) with VARVs at both nt and aa levels. Interestingly, three consecutive serine residue insertions were observed in CKBP protein of CMLV-Delhi09 isolate which was similar to CPXV-BR and VACVs, besides five point mutations (K53Q, N67I, F84S, A127T and E182G) were also similar to zoonotic OPXVs. Further, few inconsistent point mutation(s) were also observed in other gene(s) among Indian CMLVs. These indicate that different strains of CMLVs are circulating in India and these mutations could play an important role in adaptation of CMLVs in humans. The phylogeny revealed clustering of all CMLVs together except CMLV-Delhi09 which grouped separately due to the presence of specific point mutations. However, the topology of the concatenated phylogeny showed close evolutionary relationship of CMLV with VARV and TATV followed by CPXV-RatGer09/1 from Germany. The availability of this genetic information will be useful in unveiling new strategies to control emerging zoonotic poxvirus infections.
Virus Research, May 1, 2023
Reviews in Medical Virology, Jan 15, 2021
Mitogen‐activated protein kinases (MAPKs) play a key role in complex cellular processes such as p... more Mitogen‐activated protein kinases (MAPKs) play a key role in complex cellular processes such as proliferation, development, differentiation, transformation and apoptosis. Mammals express at least four distinctly regulated groups of MAPKs which include extracellular signal‐related kinases (ERK)‐1/2, p38 proteins, Jun amino‐terminal kinases (JNK1/2/3) and ERK5. p38 MAPK is activated by a wide range of cellular stresses and modulates activity of several downstream kinases and transcription factors which are involved in regulating cytoskeleton remodeling, cell cycle modulation, inflammation, antiviral response and apoptosis. In viral infections, activation of cell signalling pathways is part of the cellular defense mechanism with the basic aim of inducing an antiviral state. However, viruses can exploit enhanced cell signalling activities to support various stages of their replication cycles. Kinase activity can be inhibited by small molecule chemical inhibitors, so one strategy to develop antiviral drugs is to target these cellular signalling pathways. In this review, we provide an overview on the current understanding of various cellular and viral events regulated by the p38 signalling pathway, with a special emphasis on targeting these events for antiviral drug development which might identify candidates with broad spectrum activity.
Genome Announcements, Aug 28, 2014
The sequencing of the recombinant plasmid containing 2916 bp hexon gene insert of fowl adeno viru... more The sequencing of the recombinant plasmid containing 2916 bp hexon gene insert of fowl adeno virus 4 (FAV4) of Indian origin revealed the complete nucleotide sequence of the FAV4 hexon gene. The sequence analysis revealed an open reading frame of 2814 bp coding for a 937 amino acids long polypeptide with a molecular mass of 106.04 kDa. This sequence was larger than the hexon coding regions of FAV10, HAV40, HAV41, MAV1 and BAV3, while it was smaller than the hexon in HAV2 and HAV5. The Kozak sequence was found at nucleotide position 78, which was similar in FAV10 hexon gene. The codon bias revealed a strong preference for C and to a lesser extent G in the third base position. The splice acceptor sequence in FAV4Ind was located 12 bp upstream of the hexon initiation site of the translation codon, which indicated that FAV4 hexon could be a late gene product. A high degree of amino acid variation (9.6%) was observed between FAV4Ind and FAV10, as compared to the 1.5% variation between FAV4Ind and FAV4KR95. The L1 loop of the hexon gene showed the maximum sequence variation among FAV serotypes, thus it could be used for designing serotype specific PCR primers. The 11 unique amino acid substitutions in FAV4Ind hexon could play a significant role in determining its type specificity.
Indian Journal of Comparative Microbiology, Immunology and Infectious Diseases, 2003
195-202<span style="font-size:9.0pt;mso-ansi-language:EN-IN;mso-bidi-font-weight: bold&qu... more 195-202<span style="font-size:9.0pt;mso-ansi-language:EN-IN;mso-bidi-font-weight: bold">Virulence-associated plasmid (Vap) genes of clinical isolates of Rhodococcus equi were characterized. Isolates were identified by 16S rRNA, choE and <i style="mso-bidi-font-style: normal">traA gene PCR, followed by amplification, cloning and sequencing of 7 Vap<span style="mso-bidi-font-weight: bold"> genes. <span style="font-size:9.0pt;mso-ansi-language:EN-IN;mso-bidi-font-weight: bold">The isolates were found positive for <i style="mso-bidi-font-style: normal">vapA gene family. The comparative sequence analysis of vap genes revealed 99-100% similarity at both nt and aa levels with all sequences. The aa sequences of the predicted Vap proteins<span style="font-size: 9.0pt;mso-ansi-language:EN-IN;mso-bidi-font-weight:bold"> exhibited a high degree of similarity to each other, especially at the carboxy t...
Haryana Veterinarian, 2015
Cases of swinepox were investigated in two piggery units in Sonipat and Rohtak districts of Harya... more Cases of swinepox were investigated in two piggery units in Sonipat and Rohtak districts of Haryana state. Overall morbidity rate, cumulative mortality and case fatality rate due to the disease in both the units were 13.63%, 9.84%, 72.22%, respectively. The disease was characterized by fever, drastic decrease in feed and water intake, dullness, inability to stand and eruptions and scab formation on the skin. Swinepox virus (SWPV) was detected in scabs, spleen and lymph nodes using PCR targeting VLTF-3 gene and sequence analysis. The SWPV from India shared nucleotide identity of 98.9% and aminoacid identity of 96.6% with SWPV from Brazil. Phylogenetic analysis revealed that the SWPV from India was found to cluster closely with SWPV from Brazil with high bootstrap value. Further studies are required on its prevalence in different geographic areas as well as molecular epidemiology.
Genome announcements, Jan 22, 2015
Salmonella enterica subsp. enterica serovar Gallinarum biovar Gallinarum causes fowl typhoid (FT)... more Salmonella enterica subsp. enterica serovar Gallinarum biovar Gallinarum causes fowl typhoid (FT), which results in huge economic losses to poultry farmers in India. We report the draft genome sequence of Salmonella biovar Gallinarum strain VTCCBAA614, isolated from a chicken in an FT affected broiler flock.
Journal of Immunology and Immunopathology, 2005
A recombinant plasmid pcDNA3.1/V5-His-TOPO.fav4hex (8.5 kb) encoding the hexon gene (2916 bp) of ... more A recombinant plasmid pcDNA3.1/V5-His-TOPO.fav4hex (8.5 kb) encoding the hexon gene (2916 bp) of fowl adenovirus 4 was found to express hexon protein in transfected Vero cells as detected by immunoperoxidase test. Vaccination of 3-days old chicken with 50 mg of recombinant plasmid DNA intramuscularly revealed that the vaccinated birds' withstood challenge with 10,000 ID50 of virulent liver passaged FAV4 after 21-days of vaccination while the control (non-vaccinated) birds either died or contracted disease. The field trials of the vaccine exhibited safety and potency. The study reveals that the vaccine could be used as a candidate DNA vaccine to protect the birds against FAV4 infection.
Journal of Immunological Methods
In this study, miRNA profiling of cells infected with lumpy skin disease virus (LSDV) was conduct... more In this study, miRNA profiling of cells infected with lumpy skin disease virus (LSDV) was conducted for the first time. As compared to the mock-infected cells, LSDV-infected primary lamb testicle (LT) cells revealed dysregulation of 64, 85, and 85 miRNAs at 12 hours post-infection (hpi), 48 hpi and 72 hpi, respectively. While some of these miRNAs were found to be specifically dysregulated at a particular time point following LSDV infection, others were commonly dysregulated across all three time points. The analysis of the differentially expressed miRNA-mRNA interaction networks, Gene ontology analysis of the predicted targets and KEGG analysis of the highly enriched pathways revealed several cellular factors/pathways involved in protein/ion/enzyme binding, cell differentiation, movement of subcellular component, calcium reabsorption, aldosterone synthesis and secretion and, melanogenesis. Besides understanding virus replication, virus-host interactions and disease pathogenesis, the...
Scientific Reports
Rho-associated coiled-coil containing protein kinase 1 (ROCK1) intracellular cell signaling pathw... more Rho-associated coiled-coil containing protein kinase 1 (ROCK1) intracellular cell signaling pathway regulates cell morphology, polarity, and cytoskeletal remodeling. We observed the activation of ROCK1/myosin light chain (MLC2) signaling pathway in buffalopox virus (BPXV) infected Vero cells. ROCK1 depletion by siRNA and specific small molecule chemical inhibitors (Thiazovivin and Y27632) resulted in a reduced BPXV replication, as evidenced by reductions in viral mRNA/protein synthesis, genome copy numbers and progeny virus particles. Further, we demonstrated that ROCK1 inhibition promotes deadenylation of viral mRNA (mRNA decay), mediated via inhibiting interaction with PABP [(poly(A)-binding protein] and enhancing the expression of CCR4-NOT (a multi-protein complex that plays an important role in deadenylation of mRNA). In addition, ROCK1/MLC2 mediated cell contraction, and perinuclear accumulation of p-MLC2 was shown to positively correlate with viral mRNA/protein synthesis. Fina...
Molecular Biology and Evolution
Host-dependency factors have increasingly been targeted to minimize antiviral drug resistance. In... more Host-dependency factors have increasingly been targeted to minimize antiviral drug resistance. In this study, we have demonstrated that inhibition of p38 mitogen-activated protein kinase (a cellular protein) suppresses buffalopox virus (BPXV) protein synthesis by targeting p38-MNK1-eIF4E signaling pathway. In order to provide insights into the evolution of drug resistance, we selected resistant mutants by long-term sequential passages (P; n = 60) in the presence of p38 inhibitor (SB239063). The P60-SB239063 virus exhibited significant resistance to SB239063 as compared to the P60-Control virus. To provide mechanistic insights on the acquisition of resistance by BPXV-P60-SB239063, we generated p38-α and p38-ϒ (isoforms of p38) knockout Vero cells by CRISPR/Cas9-mediated genome editing. It was demonstrated that unlike the wild type (WT) virus which is dependent on p38-α isoform, the resistant virus (BPXV-P60-SB239063) switches over to use p38-ϒ so as to efficiently replicate in the ta...
bioRxiv, 2020
Emetine is a FDA-approved drug for the treatment of amebiasis. In the recent times we had also de... more Emetine is a FDA-approved drug for the treatment of amebiasis. In the recent times we had also demonstrated the antiviral efficacy of emetine against some RNA and DNA viruses. Following emergence of the COVID-19, we further evaluated thein vitro antiviral activity of emetine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The therapeutic index of emetine was determined to be 10910.4, at a cytotoxic concentration 50 (CC50) of 1603.8 nM and effective concentration 50 (EC50) of 0.147 nM.Besides, we also demonstrated the protective efficacy of emetine against lethal challenge with infectious bronchitis virus (IBV; a chicken coronavirus) in the embryonated chicken egg infection model. Emetine treatment was shown to decrease viral RNA and protein synthesis without affecting other steps of viral life cycle such as attachment, entry and budding.In a chromatin immunoprecipitation (CHIP) assay, emetine was shown to disrupt the binding of SARS-CoV-2 RNA with eIF4E (eukary...