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Synthetic and Semi-synthetic Drugs as a Promising Therapeutic Option for the Treatment of COVID-19

Shirbhate E, Patel P, Patel VK, Veerasamy R, Sharma PC, Sinha BN, et al.

Mini Rev Med Chem, 2021;21(8):1004-1016.
PMID: 33280595 DOI: 10.2174/1389557520666201204162103

The novel coronavirus disease-19 (COVID-19) is a global pandemic that emerged from Wuhan, China, and has spread all around the world, affecting 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 updates of August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine exists. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID- 19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in clinical uses or studies on COVID-19 and also focuses on the mode of action of drugs being repositioned against COVID-19.
The combination of histone deacetylase inhibitors and radiotherapy: a promising novel approach for cancer treatment

Shirbhate E, Patel P, Patel VK, Veerasamy R, Sharma PC, Rajak H

Future Oncol, 2020 Oct;16(30):2457-2469.
PMID: 32815411 DOI: 10.2217/fon-2020-0385

HDAC inhibitors (HDACi) play an essential role in various cellular processes, such as differentiation and transcriptional regulation of key genes and cytostatic factors, cell cycle arrest and apoptosis that facilitates the targeting of epigenome of eukaryotic cells. In the majority of cancers, only a handful of patients receive optimal benefit from chemotherapeutics. Additionally, there is emerging interest in the use of HDACi to modulate the effects of ionizing radiations. The use of HDACi with radiotherapy, with the goal of reaching dissimilar, often distinct pathways or multiple biological targets, with the expectation of synergistic effects, reduced toxicity and diminished intrinsic and acquired resistance, conveys an approach of increasing interest. In this review, the clinical potential of HDACi in combination with radiotherapy is described as an efficient synergy for cancer treatment will be overviewed.
Histone Deacetylase Inhibitors for the Treatment of Colorectal Cancer: Recent Progress and Future Prospects

Singh A, Patel P, Patel VK, Jain DK, Veerasamy R, Sharma PC, et al.

Curr Cancer Drug Targets, 2017;17(5):456-466.
PMID: 28067178 DOI: 10.2174/1568009617666170109150134

BACKGROUND: Colorectal cancer is a devastating disease with a dismal prognosis which is heavily hampered by delayed diagnosis. Surgical resection, radiation therapy and chemotherapy are the curative options. Due to few therapeutic treatments available i.e., mono and combination therapy and development of resistance towards drug response, novel and efficacious therapy are urgently needed.
OBJECTIVE: In this study, we have studied the potential of histone deacetylase inhibitors in colorectal cancer.
RESULTS: Histone deacetylase inhibitors (HDACIs) are an emerging class of therapeutic agents having potential anticancer activity with minimal toxicity for different types of malignancies in preclinical studies. HDACIs have proven less effective in monotherapy thus the combination of HDACIs with other anticancer agents are being assessed for the treatment of colorectal cancer.
CONCLUSION: The molecular mechanism emphasizing the anticancer effect of HDACIs in colorectal cancer was illustrated and a recapitulation was carried out on the recent advances in the rationale behind combination therapies currently underway in clinical evaluations.
Fulltext Corticosteroids for treatment of COVID-19: effect, evidence, expectation and extent

Patel VK, Shirbhate E, Patel P, Veerasamy R, Sharma PC, Rajak H

Beni Suef Univ J Basic Appl Sci, 2021;10(1):78.
PMID: 34751250 DOI: 10.1186/s43088-021-00165-0

Background: The World Health Organization (WHO) announced the COVID-19 occurrence as a global pandemic in March 2020. The treatment of SARS-CoV-2 patients is based on the experience gained from SARS-CoV and MERS-CoV infection during 2003. There is no clinically accepted therapeutic drug(s) accessible yet for the treatment of COVID-19.
Main body: Corticosteroids, i.e., dexamethasone, methylprednisolone, hydrocortisone and prednisone are used alone or in combination for the treatment of moderate, severe and critically infected COVID-19 patients who are hospitalized and require supplemental oxygen as per current management strategies and guidelines for COVID-19 published by the National Institutes of Health. Corticosteroids are recorded in the WHO model list of essential medicines and are easily accessible worldwide at a cheaper cost in multiple formulations and various dosage forms. Corticosteroid can be used in all age group of patients, i.e., children, adult, elderly and during pregnancy or breastfeeding women. Corticosteroids have potent anti-inflammatory and immunosuppressive effects in both primary and secondary immune cells, thereby reducing the generation of proinflammatory cytokines and chemokines and lowering the activation of T cells, monocytes and macrophages. The corticosteroids should not be used in the treatment of non-severe COVID-19 patients because corticosteroids suppress the immune response and reduce the symptoms and associated side effects such as slow recovery, bacterial infections, hypokalemia, mucormycosis and finally increase the chances of death.
Conclusion: Intensive research on corticosteroid therapy in COVID-19 treatment is urgently needed to elucidate their mechanisms and importance in contributing toward successful prevention and treatment approaches. Hence, this review emphasizes on recent advancement on corticosteroid therapy for defining their importance in overcoming SARS-CoV-2 pandemic, their mechanism, efficacy and extent of corticosteroids in the treatment of COVID-19 patients.