North Bengal Medical College

About: North Bengal Medical College is a other organization based out in Darjeeling, India. It is known for research contribution in the topics: Population & Cancer. The organization has 624 authors who have published 691 publications receiving 5492 citations.

A virus that has gone viral: Amino acid mutation in S protein of Indian isolate of Coronavirus COVID-19 might impact receptor binding and thus infectivity

Abstract: Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002, MERS-CoV in 2012, and the recent outbreak of SARS-CoV-2 late in 2019 (also named as COVID-19 or novel coronavirus 2019 or nCoV2019. Spike(S) protein, one of the structural proteins of this virus plays key role in receptor (ACE2) binding and thus virus entry. Thus, this protein has attracted scientists for detailed study and therapeutic targeting. As the 2019 novel coronavirus takes its course throughout the world, more and more sequence analyses are been done and genome sequences getting deposited in various databases. From India two clinical isolates have been sequenced and the full genome deposited in GenBank. We have performed sequence analyses of the spike protein of the Indian isolates and compared with that of the Wuhan, China (where the outbreak was first reported). While all the sequences of Wuhan isolates are identical, we found point mutations in the Indian isolates. Out of the two isolates one was found to harbour a mutation in its Receptor binding domain (RBD) at position 407. At this site arginine (a positively charged amino acid) was replaced by isoleucine (a hydrophobic amino acid that is also a C-beta branched amino acid). This mutation has been seen to change the secondary structure of the protein at that region and this can potentially alter receptor ding of the virus. Although this finding needs further validation and more sequencing, the information might be useful in rational drug designing and vaccine engineering.

Serum magnesium and stable asthma: Is there a link?

Abstract: Background: Although magnesium is used through intravenous and inhalation route in the management of asthma, actual prevalence of hypomagnesemia in asthma is not known. We conducted this study: 1) to detect the prevalence of hypomagnesemia in stable asthma and 2) to assess the significance of hypomagnesemia in these patients. Design: Prospective clinical study. Setting: Department of Respiratory Medicine, Calcutta National Medical College, Kolkata. Period of Study: Four months from January, 2007, to April, 2007. Materials and Methods: Fifty patients attending outpatients department of respiratory medicine with stable asthma were randomly selected. They were assessed clinically and their serum magnesium levels were measured. This was compared with the serum magnesium values of 45 nonasthmatic healthy controls. Results: Out of 50 patients, 14 had hypomagnesemia. Possible relationship of hypomagnesemia with tachycardia, tachypnoea, severity of asthma, medication use, and previous and future exacerbations were analyzed. Conclusion: There was statistically significant association of hypomagnesemia with tachypnoea, severe asthma, use of long-acting b2 -agonist, inhaled corticosteroids, theophylline, use of ≥ 3 medications, previous and future exacerbations but not with tachycardia or use of short-acting β2 -agonist or montelukast.

A comparative study of infusions of phenylephrine, ephedrine and phenylephrine plus ephedrine on maternal haemodynamics in elective caesarean section

Abstract: Introduction: This randomized double blind study was started with an objective of management of spinal anaesthesia-induced hypotension in elective caesarean section by combining two commonly used vasopressors - ephedrine and phenylephrine in half of their usual doses with an expectation of reducing their foetomaternal side effects. Methods: One hundred and thirty two patients were randomized into three groups to receive either 100 mg/ml phenylephrine (group-P, n=31) or 3 mg/ml ephedrine (group-E, n=33) or 50 mg phenylephrine plus 1.5 mg ephedrine/ml (group-PE, n=29). Immediately after spinal injection the study solution was started prophylactically in every patient at the rate of 40 ml/h. A predefined algorithm was used to adjust the infusion rate according to the systolic blood pressure (SBP). Results: Mean fall of SBP was significantly more in group-E than group-P (P=0.009) and group-PE (P=0.013). This was not significantly different when compared between group-P and group-PE (P=0.9). Episodes of hypotension and tachycardia were more in group-E than the other two groups. Statistically significant tachycardia was seen in Group-E than that in other two groups. Incidence of bradycardia and hypertension did not differ significantly among the groups. Maternal nausea and Apgar score were also comparable in three groups. Conclusion: Current study claims that prophylactic phenylephrine 100 mg/ml is a better choice than ephedrine (3 mg/ml) or 50 mcg phenylephrine plus 1.5 mg ephedrine/ml in prevention of spinal anaesthesia-induced hypotension in elective caesarean section. Combination of two drugs in half the usual dose has no added advantage over phenylephrine, but this is better than ephedrine alone.

Specific mutations in SARS-CoV2 RNA dependent RNA polymerase and helicase alter protein structure, dynamics and thus function: Effect on viral RNA replication

Abstract: The open reading frame (ORF) 1ab of SARS-CoV2 encodes non-structural proteins involved in viral RNA functions like translation and replication including nsp1-4; 3C like proteinase; nsp6-10; RNA dependent RNA polymerase (RdRp); helicase and exonuclease. Sequence analyses of ORF1ab unravelled emergence of mutations especially in the viral RdRp and helicase at specific positions, both of which are important in mediating viral RNA replication. Since proteins are dynamic in nature and their functions are governed by the molecular motions, we performed normal mode analyses of the SARS-CoV2 wild type and mutant RdRp and helicases to understand the effect of mutations on their structure, conformation, dynamics and thus function. Structural analyses revealed that mutation of RdRp (at position 4715 in the context of the polyprotein/ at position 323 of RdRp) leads to rigidification of structure and that mutation in the helicase (at position 5828 of polyprotein/ position 504) leads to destabilization increasing the flexibility of the protein structure. Such structural modifications and protein dynamics alterations might alter unwinding of complex RNA stem loop structures, the affinity/ avidity of polymerase RNA interactions and in turn the viral RNA replication. The mutation analyses of proteins of the SARS-CoV2 RNA replication complex would help targeting RdRp better for therapeutic intervention.