COMPARATIVE EFFICACY OF VARIOUS ANTICOAGULANTS IN COVID-19 INDIAN SUBJECTS: AN OBSERVATIONAL STUDY

Background: To assess the efficacy of various anticoagulants being prescribed in the COVID 19 induced hypercoagulability, so as to know optimally effective anticoagulant. Methods: This was a Indian observational study conducted in our covid centre at vijayawada,Andhra Pradesh between june 2020 to January 2021 . Results: A total of 100 COVID 19 subjects were included. The patients were found to be matched with respect to age, gender, diet and past history of various illnesses. Gender wise more males (60 patients)are affected when compared to females(40 patients). Age group more affected are less than or equal to 50yrs . Comorbidites like Diabetes(67patients),cardiac problems(62patients), dyslipidemia(62patients) were seen. Risk factors like smoking(52patients), alcoholism(50patients) noticed. Almost all subjects are RTPCR positive. IL- 6,CRP,LDH high in most subjects. Ferritin and PT/INR are normal in more subjects. Out of 100 patients oxygen is required in 48 subjects and BIPAP/CPAP required in 26 subjects. Death occurred in 24 patients (2 with CVA,22 with myocardial infraction). Mortality rate is more in vegetarians. More patients in our study belongs to CORADS score 4 and 5. D-dimer are increased in 67subjects. IL-6 are increased in 68patients . Frequency of subjects with raised D-dimer (p = 0.049) and CRP (p = 0.002) levels were found to be benefitted on receiving nattokinase. However, no other parameters such as IL-6 (p = 0.068) ferritin (p = 0.396), ESR (p = 0.278), PT/INR (p = 0.47) LDH (p = 0.34) or CORADS staging achieved such significant association. Also need of interventions such as Oxygen (p = 0.001), BIPAP/CPAP (p < 0.0001) were low in patients on nattokinase. No significant difference was noted in follow up investigations such as PT/INR (p = 0.31) and other markers (D-dimer, IL-6, LDH, CRP) (p = 0.55). No bleeding episodes were reported in subjects on nattokinase. Significant low rate of death was found in subjects who received nattokinase (p < 0.0001) and rivaroxaban (p < 0.0001). Also, significantly higher mortality rate was observed in subjects who required to be put on oxygen (p < 0.0001) as well as BIPAP/CPAP (p < 0.0001). Conclusions: Nattokinase simultaneously effects several key favourable benefits for thrombosis, hypertension, atherosclerosis, hyperlipidaemia, platelet aggregation, and neuroprotection in patients with COVID 19 infection. (Figure Presented).

Development of a novel peptide inhibitor of subtilisin BPN'.

Proteinaceous protease inhibitors can strongly and specifically inhibit cognate proteases, but their use as pharmaceuticals is limited by their size. As such, the development of effective protease peptide inhibitors would be beneficial for biochemical studies and drug discovery. In this study, we applied a phage display system to select subtilisin BPN'-binding peptides and evaluated their inhibitory activities against subtilisin BPN'. A 12mer peptide with an intramolecular disulfide bond inhibited subtilisin BPN' (Ki value of 13.0 nm). Further mutational analyses of the peptide resulted in the development of a short peptide inhibitor against subtilisin BPN' that showed high inhibitory activity and binding affinity (Ki value of 0.30 nm). This activity was found to be derived from the conformational rigidity caused by the intramolecular disulfide bond and the small residue at the P1' site and from the interaction of the P4 and P6' residues with subtilisin BPN'.

Targeting the Plasmodium falciparum proteome and organelles for potential antimalarial drug candidates.

There is an unmet need to unearth alternative treatment options for malaria, wherein this quest is more pressing in recent times due to high morbidity and mortality data arising mostly from the endemic countries coupled with partial diversion of attention from the disease in view of the SARS-Cov-2 pandemic. Available therapeutic options for malaria have been severely threatened with the emergence of resistance to almost all the antimalarial drugs by the Plasmodium falciparum parasite in humans, which is a worrying situation. Artemisinin combination therapies (ACT) that have so far been the mainstay of malaria have encountered resistance by malaria parasite in South East Asia, which is regarded as a notorious ground zero for the emergence of resistance to antimalarial drugs. This review analyzes a few key druggable targets for the parasite and the potential of specific inhibitors to mitigate the emerging antimalarial drug resistance problem by providing a concise assessment of the essential proteins of the malaria parasite that could serve as targets. Moreover, this work provides a summary of the advances made in malaria parasite biology and the potential to leverage these findings for antimalarial drug production.