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Article ; Online: Evolutionary shift from purifying selection towards divergent selection of SARS-CoV2 favors its invasion into multiple human organs.

Maiti, Amit K

2022 Volume 313, Page(s) 198712

Abstract: SARS-CoV2 virus is believed to be originated from a closely related bat Coronavirus RaTG13 lineage and uses its key entry-point residues in S1 protein to attach with human ACE2 receptor. SARS-CoV2 could enter human from bat with its poorly developed ... ...

Abstract	SARS-CoV2 virus is believed to be originated from a closely related bat Coronavirus RaTG13 lineage and uses its key entry-point residues in S1 protein to attach with human ACE2 receptor. SARS-CoV2 could enter human from bat with its poorly developed entry-point residues much before its known appearance with slower mutation rate or recently with efficiently developed entry-point residues with higher mutation rate or through an intermediate host. Temporal analysis of SARS-CoV2 genome shows that its nucleotide substitution rate is as low as 27nt/year with an evolutionary rate of 9×10
MeSH term(s)	COVID-19 ; Humans ; Mutation ; RNA, Viral ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/chemistry
Chemical Substances	RNA, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-02-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605780-9
ISSN	1872-7492 ; 0168-1702
ISSN (online)	1872-7492
ISSN	0168-1702
DOI	10.1016/j.virusres.2022.198712
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Therapeutic Challenges in COVID-19.

Maiti, Amit K

Current molecular medicine

2022 Volume 24, Issue 1, Page(s) 14–25

Abstract: SARS-CoV2 is a novel respiratory coronavirus and, understanding its molecular mechanism is a prerequisite to developing effective treatment for COVID-19. This RNA genome-carrying virus has a protein coat with spikes (S) that attaches to the ACE2 receptor ...

Abstract	SARS-CoV2 is a novel respiratory coronavirus and, understanding its molecular mechanism is a prerequisite to developing effective treatment for COVID-19. This RNA genome-carrying virus has a protein coat with spikes (S) that attaches to the ACE2 receptor at the cell surface of human cells. Several repurposed drugs are used to treat COVID-19 patients that are proven to be largely unsuccessful or have limited success in reducing mortalities. Several vaccines are in use to reduce the viral load to prevent developing symptoms. Major challenges to their efficacy include the inability of antibody molecules to enter cells but remain effective in the bloodstream to kill the virus. The efficacy of vaccines also depends on their neutralizing ability to constantly evolve new virus strains due to novel mutations and evolutionary survival dynamics. Taken together, SARS-CoV2 antibody vaccines may not be very effective and other approaches based on genetic, genomic, and protein interactome could be fruitful to identify therapeutic targets to reduce disease-related mortalities.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; RNA, Viral ; Vaccines
Chemical Substances	RNA, Viral ; Vaccines
Language	English
Publishing date	2022-12-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2064873-X
ISSN	1875-5666 ; 1566-5240
ISSN (online)	1875-5666
ISSN	1566-5240
DOI	10.2174/1566524023666221222162641
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Identification of G-quadruplex DNA sequences in SARS-CoV2.

Maiti, Amit K

Immunogenetics

2022 Volume 74, Issue 5, Page(s) 455–463

Abstract: G-quadruplex structure or Putative Quadruplex Sequences (PQSs) are abundant in human, microbial, DNA, or RNA viral genomes. These sequences in RNA viral genome play critical roles in integration into human genome as LTR (Long Terminal Repeat), genome ... ...

Abstract	G-quadruplex structure or Putative Quadruplex Sequences (PQSs) are abundant in human, microbial, DNA, or RNA viral genomes. These sequences in RNA viral genome play critical roles in integration into human genome as LTR (Long Terminal Repeat), genome replication, chromatin rearrangements, gene regulation, antigen variation (Av), and virulence. Here, we investigated whether the genome of SARS-CoV2, an RNA virus, contained such potential G-quadruplex structures. Using bioinformatic tools, we searched for such sequences and found thirty-seven (forward strand (twenty-five) + reverse strand (Twelve)) QGRSs (Quadruplex forming G-Rich Sequences)/PQSs in SARS-CoV2 genome. These sequences are dispersed mainly in the upstream of SARS-CoV2 genes. We discuss whether existing PQS/QGRS ligands could inhibit the SARS-CoV2 replication and gene transcription as has been observed in other RNA viruses. Further experimental validation would determine the role of these G-quadruplex sequences in SARS-CoV2 genome function to survive in the host cells and identify therapeutic agents to destabilize these PQSs/QGRSs.
MeSH term(s)	COVID-19/genetics ; DNA ; G-Quadruplexes ; Humans ; RNA, Viral/chemistry ; RNA, Viral/genetics ; SARS-CoV-2/genetics
Chemical Substances	RNA, Viral ; DNA (9007-49-2)
Language	English
Publishing date	2022-03-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	186560-2
ISSN	1432-1211 ; 0093-7711
ISSN (online)	1432-1211
ISSN	0093-7711
DOI	10.1007/s00251-022-01257-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Development of Biomarkers and Molecular Therapy Based on Inflammatory Genes in Diabetic Nephropathy.

Maiti, Amit K

International journal of molecular sciences

2021 Volume 22, Issue 18

Abstract: Diabetic Nephropathy (DN) is a debilitating consequence of both Type 1 and Type 2 diabetes affecting the kidney and renal tubules leading to End Stage Renal Disease (ESRD). As diabetes is a world epidemic and almost half of diabetic patients develop DN ... ...

Abstract	Diabetic Nephropathy (DN) is a debilitating consequence of both Type 1 and Type 2 diabetes affecting the kidney and renal tubules leading to End Stage Renal Disease (ESRD). As diabetes is a world epidemic and almost half of diabetic patients develop DN in their lifetime, a large group of people is affected. Due to the complex nature of the disease, current diagnosis and treatment are not adequate to halt disease progression or provide an effective cure. DN is now considered a manifestation of inflammation where inflammatory molecules regulate most of the renal physiology. Recent advances in genetics and genomic technology have identified numerous susceptibility genes that are associated with DN, many of which have inflammatory functions. Based on their role in DN, we will discuss the current aspects of developing biomarkers and molecular therapy for advancing precision medicine.
MeSH term(s)	Animals ; Autophagy/genetics ; Biomarkers/metabolism ; Diabetic Nephropathies/drug therapy ; Diabetic Nephropathies/epidemiology ; Diabetic Nephropathies/genetics ; Diabetic Nephropathies/pathology ; Humans ; Inflammation/genetics ; Molecular Targeted Therapy ; Mutation/genetics
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-09-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22189985
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Evolutionary shift from purifying selection towards divergent selection of SARS-CoV2 favors its invasion into multiple human organs

Maiti, Amit K

Virus research. 2022 May, v. 313

2022

Abstract	SARS-CoV2 virus is believed to be originated from a closely related bat Coronavirus RaTG13 lineage and uses its key entry-point residues in S1 protein to attach with human ACE2 receptor. SARS-CoV2 could enter human from bat with its poorly developed entry-point residues much before its known appearance with slower mutation rate or recently with efficiently developed entry-point residues with higher mutation rate or through an intermediate host. Temporal analysis of SARS-CoV2 genome shows that its nucleotide substitution rate is as low as 27nt/year with an evolutionary rate of 9×10⁻⁴/site/year, which is well within the range of other RNA virus (10⁻⁴ to 10⁻⁶/site/year). TMRCA of SARS-CoV2 from bat RaTG13 lineage appears to be in between 9 and 14 years. Evolution of a critical entry-point residue Y493Q needs two substitutions with an intermediate virus carrying Y493H (Y>H>Q) but has not been identified in known twenty-nine bat CoV virus. Genetic codon analysis indicates that SARS-CoV2 evolution during propagation in human disobeys neutral evolution as nonsynonymous mutations surpass synonymous mutations with the increase of ω (dₙ/dₛ). Taken together, genetic data suggests that SARS-CoV2 is originated long time back before its appearance in human in 2019. Increase of ω signifies that SARs-CoV2 evolution is approaching towards diversifying selection from purifying selection predictably for its infection power to evade multiple human organs.
Keywords	Chiroptera ; Orthocoronavirinae ; genome ; humans ; intermediate hosts ; mutation rate ; research ; viruses
Language	English
Dates of publication	2022-05
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	605780-9
ISSN	1872-7492 ; 0168-1702
ISSN (online)	1872-7492
ISSN	0168-1702
DOI	10.1016/j.virusres.2022.198712
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The African-American population with a low allele frequency of SNP rs1990760 (T allele) in IFIH1 predicts less IFN-beta expression and potential vulnerability to COVID-19 infection.

Maiti, Amit K

Immunogenetics

2020 Volume 72, Issue 6-7, Page(s) 387–391

Abstract: Covid-19 has caused worldwide devastation. IFIH1 is a pattern recognition receptor that senses coronavirus RNA and triggers interferon production as a first line of viral immune defense. The role of IFIH1 polymorphism, rs1990760 (C>T; aaA946T) in the ... ...

Abstract	Covid-19 has caused worldwide devastation. IFIH1 is a pattern recognition receptor that senses coronavirus RNA and triggers interferon production as a first line of viral immune defense. The role of IFIH1 polymorphism, rs1990760 (C>T; aaA946T) in the epidemiology of viral infection is well studied, and the minor allele T resists viral infection. Knock-in mice with mutated IFIH1 protein (946T) for this allele have enhanced interferon production and protection from lethal viral infection. The minor allele frequency (Tmaf) varies widely from Africans (0.06 to 0.35) to Chinese (0.19 to 0.23) to Caucasians (0.56 to 0.69). During the initial days of infection when the social restrictions were not imposed, I show that the infection rate in Italy was lower as expected from its higher Tmaf (0.56) than that in China (Tmaf for southern China, 0.23). The infection rate in the USA and Spain was intermediate between those two countries despite higher Caucasian overall Tmaf (0.69), perhaps due to a more admixed African population in these countries. These analyses suggest that African-Americans and Chinese with low Tmaf of rs1990760 are more vulnerable to SARS-COV2 infection, apart from other genetic factors or socioeconomic conditions in these population. Taken together, an IFN-beta supplement might aid in preventing COVID-19 infection and help in development of herd immunity.
MeSH term(s)	African Americans/genetics ; Asian Continental Ancestry Group ; Betacoronavirus ; COVID-19 ; China ; Coronavirus Infections/genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Interferon-Induced Helicase, IFIH1/genetics ; Interferon-beta ; Italy ; Pandemics ; Pneumonia, Viral/genetics ; Polymorphism, Single Nucleotide ; SARS-CoV-2 ; United States
Chemical Substances	Interferon-beta (77238-31-4) ; IFIH1 protein, human (EC 3.6.1.-) ; Interferon-Induced Helicase, IFIH1 (EC 3.6.4.13)
Keywords	covid19
Language	English
Publishing date	2020-07-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	186560-2
ISSN	1432-1211 ; 0093-7711
ISSN (online)	1432-1211
ISSN	0093-7711
DOI	10.1007/s00251-020-01174-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Development of Biomarkers and Molecular Therapy Based on Inflammatory Genes in Diabetic Nephropathy

Amit K. Maiti

International Journal of Molecular Sciences, Vol 22, Iss 9985, p

2021 Volume 9985

Abstract	Diabetic Nephropathy (DN) is a debilitating consequence of both Type 1 and Type 2 diabetes affecting the kidney and renal tubules leading to End Stage Renal Disease (ESRD). As diabetes is a world epidemic and almost half of diabetic patients develop DN in their lifetime, a large group of people is affected. Due to the complex nature of the disease, current diagnosis and treatment are not adequate to halt disease progression or provide an effective cure. DN is now considered a manifestation of inflammation where inflammatory molecules regulate most of the renal physiology. Recent advances in genetics and genomic technology have identified numerous susceptibility genes that are associated with DN, many of which have inflammatory functions. Based on their role in DN, we will discuss the current aspects of developing biomarkers and molecular therapy for advancing precision medicine.
Keywords	diabetes ; nephropathy ; inflammation ; genes ; biomarker ; precision therapy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The African-American population with a low allele frequency of SNP rs1990760 (T allele) in IFIH1 predicts less IFN-beta expression and potential vulnerability to COVID-19 infection

Maiti, Amit K.

Immunogenetics

2020 Volume 72, Issue 6-7, Page(s) 387–391

Keywords	Immunology ; Genetics ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
ZDB-ID	186560-2
ISSN	1432-1211 ; 0093-7711
ISSN (online)	1432-1211
ISSN	0093-7711
DOI	10.1007/s00251-020-01174-6
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The African-American population with a low allele frequency of SNP rs1990760 (T allele) in IFIH1 predicts less IFN-beta expression and potential vulnerability to COVID-19 infection

Maiti, Amit K

Immunogenetics

Abstract	Covid-19 has caused worldwide devastation. IFIH1 is a pattern recognition receptor that senses coronavirus RNA and triggers interferon production as a first line of viral immune defense. The role of IFIH1 polymorphism, rs1990760 (C>T; aaA946T) in the epidemiology of viral infection is well studied, and the minor allele T resists viral infection. Knock-in mice with mutated IFIH1 protein (946T) for this allele have enhanced interferon production and protection from lethal viral infection. The minor allele frequency (Tmaf) varies widely from Africans (0.06 to 0.35) to Chinese (0.19 to 0.23) to Caucasians (0.56 to 0.69). During the initial days of infection when the social restrictions were not imposed, I show that the infection rate in Italy was lower as expected from its higher Tmaf (0.56) than that in China (Tmaf for southern China, 0.23). The infection rate in the USA and Spain was intermediate between those two countries despite higher Caucasian overall Tmaf (0.69), perhaps due to a more admixed African population in these countries. These analyses suggest that African-Americans and Chinese with low Tmaf of rs1990760 are more vulnerable to SARS-COV2 infection, apart from other genetic factors or socioeconomic conditions in these population. Taken together, an IFN-beta supplement might aid in preventing COVID-19 infection and help in development of herd immunity.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #690803
Database	COVID19

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Article ; Online: Using multiscale molecular dynamics simulations to obtain insights into pore forming toxin mechanisms.

Desikan, Rajat / Behera, Amit / Maiti, Prabal K / Ayappa, K Ganapathy

Methods in enzymology

2021 Volume 649, Page(s) 461–502

Abstract: Pore forming toxins (PFTs) are virulent proteins released by several species, including many strains of bacteria, to attack and kill host cells. In this article, we focus on the utility of molecular dynamics (MD) simulations and the molecular insights ... ...

Abstract	Pore forming toxins (PFTs) are virulent proteins released by several species, including many strains of bacteria, to attack and kill host cells. In this article, we focus on the utility of molecular dynamics (MD) simulations and the molecular insights gleaned from these techniques on the pore forming pathways of PFTs. In addition to all-atom simulations which are widely used, coarse-grained MARTINI models and structure-based models have also been used to study PFTs. Here, the emphasis is on methods and techniques involved while setting up, monitoring, and evaluating properties from MD simulations of PFTs in a membrane environment. We draw from several case studies to illustrate how MD simulations have provided molecular insights into protein-protein and protein-lipid interactions, lipid dynamics, conformational transitions and structures of both the oligomeric intermediates and assembled pore structures.
MeSH term(s)	Lipid Bilayers ; Molecular Conformation ; Molecular Dynamics Simulation
Chemical Substances	Lipid Bilayers
Language	English
Publishing date	2021-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1557-7988
ISSN (online)	1557-7988
DOI	10.1016/bs.mie.2021.01.021
Database	MEDical Literature Analysis and Retrieval System OnLINE

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