Publications by authors named "Aurosikha Das"

2 Publications

  • Page 1 of 1

The role of human C5a as a non-genomic target in corticosteroid therapy for management of severe COVID19.

Comput Biol Chem 2021 Jun 5;92:107482. Epub 2021 Apr 5.

Chemical Biology Laboratory, School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Odisha, 752050, India. Electronic address:

Complement system plays a dual role; physiological as well as pathophysiological. While physiological role protects the host, pathophysiological role can substantially harm the host, by triggering several hyper-inflammatory pathways, referred as "hypercytokinaemia". Emerging clinical evidence suggests that exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), tricks the complement to aberrantly activate the "hypercytokinaemia" loop, which significantly contributes to the severity of the COVID19. The pathophysiological response of the complement is usually amplified by the over production of potent chemoattractants and inflammatory modulators, like C3a and C5a. Therefore, it is logical that neutralizing the harmful effects of the inflammatory modulators of the complement system can be beneficial for the management of COVID19. While the hunt for safe and efficacious vaccines were underway, polypharmacology based combination therapies were fairly successful in reducing both the morbidity and mortality of COVID19 across the globe. Repurposing of small molecule drugs as "neutraligands" of C5a appears to be an alternative for modulating the hyper-inflammatory signals, triggered by the C5a-C5aR signaling axes. Thus, in the current study, few specific and non-specific immunomodulators (azithromycin, colchicine, famotidine, fluvoxamine, dexamethasone and prednisone) generally prescribed for prophylactic usage for management of COVID19 were subjected to computational and biophysical studies to probe whether any of the above drugs can act as "neutraligands", by selectively binding to C5a over C3a. The data presented in this study indicates that corticosteroids, like prednisone can have potentially better selectively (K ∼ 0.38 μM) toward C5a than C3a, suggesting the positive modulatory role of C5a in the general success of the corticosteroid therapy in moderate to severe COVID19.
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http://dx.doi.org/10.1016/j.compbiolchem.2021.107482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020607PMC
June 2021

Resveratrol binding to human complement fragment 5a (C5a) may modulate the C5aR signaling axes.

J Biomol Struct Dyn 2021 Mar 17;39(5):1766-1780. Epub 2020 Mar 17.

Chemical Biology Laboratory, School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, Odisha, India.

Resveratrol (RSV), the active pharmaceutical ingredient (API) found in several fruits, nuts and marketed nutraceuticals is one of the promiscuous phytoalexin known to promote good health. The health benefits of RSV could be due to its antioxidant activity or its direct interaction with target proteins, resulting modulation of several cells signaling and inflammatory pathways. Among many of its disease preventing activities, RSV has been shown to ameliorate inflammation by directly binding the COX-1 and COX-2 enzymes, the established targets of common non-steroidal anti-inflammatory drugs (NSAIDs). As a follow up to our recent study, we have now identified that RSV can also directly target C5a, a pro-inflammatory glycoprotein of the complement system, whose upregulation has been linked to exacerbate the chronic inflammation induced diseases, by recruitment of C5a receptor (C5aR) expressed in both immune and non-immune cells. The data derived from the molecular dynamics, automated docking and binding free energy calculation as well as from the circular dichroism, and steady state fluorescence studies indicate that glycosylation of C5a may not alter its structure significantly and further confirms that RSV strongly bind to the C5a, which may be responsible for the anti-inflammatory activity demonstrated by RSV in C5a-C5aR induced inflammatory pathways.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1738958DOI Listing
March 2021
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