Day :
- Corona Virus
Location: Montreal, Canada
Session Introduction
Pratibha M.
Indian Institute of Technology Hyderabad, Sangareddy, Telengana, India
Title: Spike protein of SARS-CoV-2: Impact of single amino acid mutation and effect of drug binding to the variant-insilico analysis.
Biography:
I am Pratibha M. currently doing my M.Tech in medical biotechnology at IITH. I have done my B.Tech at PSG College of Technology, Coimbatore on Biotechnology. I hold one year work experience on recombinant protein production and secondary metabolite production from microbes. I have done my UG final year project at Anthem Biosciences, Bangalore. I have qualified GATE examination in the year of 2019 with 94 percentile.
Abstract:
Novel SARS-CoV-2, a bat based virus originated in Wuhan, China caused a global pandemic in December, 2019 belongs to the Betacorona virus family. This virus mostly enters into the respiratory tract of human and enters into the cell through Angiotensin Convertase II (ACE2) receptor which is present in the epithelial layers. SARS-CoV-2 containing a single stranded RNA genome (~29Kbp) enters the cell with the help of Spike (S) protein. Spike protein is a glycoprotein responsible for receptor binding and membrane fusion. The S1 domain of spike protein has an N terminal domain (NTD) and a C-Terminal Domain (CTD). CTD is the receptor binding site. Binding is facilitated when the host cell secretes TMPRSS2 serine protease which cleaves the S1/S2 boundary of spike protein and due to this cleavage, S2 domain undergoes conformational changes and thereby it facilitates the membrane fusion of virus to host cell. Multiple sequence alignment of the spike protein sequence of SARS-CoV-2 shows the number of single amino acid mutation hotspots such as L5F, R214L, R408I, G476S, V483A, H519Q, A520S, T572I, D614G and H655Y. Among these mutations D14G has 57.5% occurrence and G476S, V483A has 7.5% occurrence. The mutated sequences were structured and docked to ACE2 receptor using bioinformatics tool. When the mutated S protein is docked, the ∆G (free energy) value is very minimal in mutated protein and the dissociation constant (Kd) value is higher showed the stability of variants. By the drug repurposing method, 1000 FDA approved drugs were virtually screened for its binding to RBD of S1 domain. Among these Digitoxin, Gliquidone and Zorubicin Hcl binds to spike proteins with more than -8.5 Kcal/mol to both wild type and mutants.
- Viral Immunology and Immunopathology
Location: Montreal, Canada
Session Introduction
Xueqing Wang
3School of Medical and Health Sciences, Edith Cowan University Perth 6027, WA, Australia
Title: Viral Immunology and Immunopathology
Biography:
Ms Xueqing Wang is a PhD Candaidate from the School of Medical and Health Sciences at Edith Cowan University. Her PhD Project is ‘How Coxsackievirus B3 Infection Acts as a Risk Factor for Type 2 Diabetes Mellitus by Triggering Autophagy and Persistent Inflammation’. She has published 5 papers as the co-author in reputed journals and won the 2nd price in the australian academic transformation speech contest, Alpha Innovation Contest 2019
Abstract:
Coxsackievirus group B (CVB) is considered as one of the most common pathogens of human viral myocarditis. CVB-induced myocarditis is mainly characterized by the persistence of the virus infection and immune-mediated inflammatory injury. Costimulatory signals are crucial for the activation of adaptive immunity. Our data reveal that the CVB type 3 (CVB3) infection altered the expression profile of costimulatory molecules in host cells. CVB3 infection caused the decrease of PD-1 ligand expression, partially due to the cleavage of AU-rich element binding protein AUF1 by the viral protease 3Cpro, leading to the exacerbated inflammatory injury of the myocardium. Moreover, systemic PD-L1 treatment, which augmented the apoptosis of proliferating lymphocytes, alleviated myocardial inflammatory injury. Our findings suggest that PD1-pathway can be a potential immunologic therapeutic target for CVB-induced myocarditis.
- Clinical and Neuro Virology
Location: Montreal, Canada
Session Introduction
Dr.Shahroz Khan
Noor Nursing College Daggar Buner, KPK, Pakistan
Title: Molecular diagnosis of hepatitis C untypeable genotypes among chronically infected patients in Pakistan
Biography:
Dr.Shahroz Khan has completed his PhD at the age of 34 years from Quaid-i-Azam University in Molecular Virology. He is Asisstant Professor at Noor Nursing College Daggar Buner. He has published more than 25 papers in good journals.
Abstract:
The objective of the study was to characterize the Untypable HCV
isolates from various geographical areas of Pakistan by sequencing and phylogenetic analysis of
their 5′UTRs. The emergence of large number of HCV Untypable isolates among chronically
infected Pakistani subjects pose challenges to accurate diagnosis, optimal regimen, dose and
duration of antiviral therapy as well as for estimating the response rate. During the course of this
study, a total of 415 Untypable HCV strains were detected from different parts of the country in
which 50 (12%) randomly selected serum samples were used for sequence analysis of 5′UTR of
HCV. The derived consensus sequences in case of all the 50 isolates were later used for genotype
prediction using NCBI BLAST (ncbi.nlm.nih.gov) and online HCV genotype prediction tools.
The results indicated that all the 50 samples (100%) were very close to HCV 3a. Self-alignment
of all the 5' UTR sequences identified 10 diverse types circulating in Pakistan. Most common
sequence variations were conserved (*), deletion (-) and transversion. Phylogenetic analysis of
HCV Untypable isolates based on the 5' UTR sequences indicated that most of these isolates
were genetically closer to Pakistani HCV 3a isolates with high bootstrap value as compared to
some regional isolates. However, One Untypable isolate PK3 clustered with isolates from other
regions and was distant from the Pakistani isolates which indicates that HCV 3a of different
origins are distinctly evolving in Pakistan. The genetic diversity and phylogenetic analysis point
towards the rise of variants of HCV 3a in this region in the form of the Untypable strains which
need through characterization.
- Novel Antiviral Therapies
Location: Montreal, Canada
Session Introduction
Dr. Nidhi Kaushik
SRM University, Delhi NCR, India
Title: Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase.
Biography:
Dr. Nidhi Kaushik has completed her PhD at the age of 30, from Translational Health Science and Technology Institute, India. She is teaching as an Assistant Professor in SRM University, delhi NCR, India. She has published six papers in reputed journals.
Abstract:
Hepatitis E virus (HEV) causes an acute, self-limiting hepatitis in healthy individuals and leads to chronic disease in immunocompromised individuals. HEV infection in pregnant women results in a more severe outcome, with the mortality rate going up to 30%. Though the virus usually causes sporadic infection, epidemics have been reported in developing and resource-starved countries. No specific antiviral exists against HEV. A combination of interferon and ribavirin therapy has been used to control the disease with some success. Zinc is an essential micronutrient that plays crucial roles in multiple cellular processes. Zinc salts are known to be effective in reducing infections caused by few viruses. Here, we investigated the effect of zinc salts on HEV replication. In a human hepatoma cell (Huh7) culture model, zinc salts inhibited the replication of genotype 1 (g-1) and g-3 HEV replicons and g-1 HEV infectious genomic RNA in a dose-dependent manner. Analysis of a replication-defective mutant of g-1 HEV genomic RNA under similar conditions ruled out the possibility of zinc salts acting on replication-independent processes. An ORF4-Huh7 cell line-based infection model of g-1 HEV further confirmed the above observations. Zinc salts did not show any effect on the entry of g-1 HEV into the host cell. Furthermore, our data reveal that zinc salts directly inhibit the activity of viral RNA-dependent RNA polymerase (RdRp), leading to inhibition of viral replication. Taken together, these studies unravel the ability of zinc salts in inhibiting HEV replication, suggesting their possible therapeutic value in controlling HEV infection. Hepatitis E virus (HEV) is a public health concern in resource-starved countries due to frequent outbreaks. It is also emerging as a health concern in developed countries owing to its ability to cause acute and chronic infection in organ transplant and immunocompromised individuals. Although antivirals such as ribavirin have been used to treat HEV cases, there are known side effects and limitations of such therapy. Our discovery of the ability of zinc salts to block HEV replication by virtue of their ability to inhibit the activity of viral RdRp is important because these findings pave the way to test the efficacy of zinc supplementation therapy in HEV-infected patients. Since zinc supplementation therapy is known to be safe in healthy individuals and since high-dose zinc is used in the treatment of Wilson's disease, it may be possible to control HEV-associated health problems following a similar treatment regimen.