In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2

Chauhan

Expert Review of Clinical Pharmacology

et al. 2021

Introduction : The global coronavirus disease-2019 (COVID-19) pandemic has posed a critical challenge to the research community as well as to the healthcare systems. Severe COVID-19 patients are at a higher risk of developing serious complications and mortality. There is a dire need for safe and effective pharmacotherapy for addressing unmet needs of these patients. Concomitant use of dexamethasone and tetracyclines, by virtue of their immunomodulatory and other relevant pharmacological properties, offers a potential strategy for synergy aimed at improving clinical outcomes. Areas covered : Here we review the potential benefits of combining dexamethasone and tetracyclines (minocycline or doxycycline) for the management of severe COVID-19 patients. We have critically examined the evidence obtained from in silico, experimental, and clinical research. We have also discussed the plausible mechanisms, advantages, and drawbacks of this proposed combination therapy for managing severe COVID-19. Expert opinion : The concomitant use of dexamethasone and one of the tetracyclines among severe COVID-19 patients offers several advantages in terms of additive immunomodulatory effects, cost-effectiveness, wide-availability, and well-known pharmacological properties including adverse-effect profile and contraindications. There is an urgent need to facilitate pilot studies followed by well-designed and adequately-powered multicentric clinical trials to generate conclusive evidence related to utility of this approach.

Section: Tetracyclines: Potential In Covid-19 Managementmentioning

confidence: 99%

Section: Benefits and Drawbacks Of Concomitant Use Of Dexamethasone Amentioning

confidence: 99%

Concomitant use of dexamethasone and tetracyclines: a potential therapeutic option for the management of severe COVID-19 infection?

Chauhan

Expert Review of Clinical Pharmacology

et al. 2021

“…EXPT00713 (DB03648) is a P. falciparum formylmethionine deformylase inhibitor with a reported IC 50 of 130 nM . Interestingly, several antimalarial drugs are under the spotlight of COVID-19 investigations (Gendrot et al, 2020).…”

Section: Candidates For Drug Repurposingmentioning

confidence: 99%

Drug repurposing and polypharmacology to fight SARS-CoV-2 through the inhibition of the main protease

Pinzi

Tinivella

Caporuscio

et al. 2020

Preprint

Therapeutic options are urgently needed to fight the outbreak of a novel coronavirus (SARS-CoV-2), which causes the COVID-19 disease and is spreading rapidly around the world. Drug repurposing can significantly accelerate the identification of drug candidates suitable for clinical evaluation. Moreover, polypharmacological effects may increase antiviral activity and/or counteract severe complications concurrently affecting COVID-19 patients. Herein, we present the results of a computational drug repurposing campaign in search of potential inhibitors of the main protease of SARS-CoV-2. The screening allowed the selection of 22 promising drugs. Some of them have already entered clinical trials, but the vast majority of the identified compounds are new and have never been considered before. For each repurposed compound, its therapeutic relevance and potential beneficial polypharmacological effects that may arise due to its original therapeutic indication are thoroughly discussed.

Pulmonary Pharmacology & Therapeutics

“…For example, Fredeking et al [ 18 ] illustrated that doxycycline reduces pro-inflammatory cytokines in patients with dengue hemorrhagic fever. Furthermore, different reports disclosed the potential benefit of doxycycline therapy in the management of COVID-19 due to its anti-inflammatory and anti-SARS-CoV-2 activities [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Sequential doxycycline and colchicine combination therapy in Covid-19: The salutary effects

Al-Kuraishy

Al-Gareeb

Qusty

et al. 2021

Coronavirus virus disease 2019 (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), actually considered as a global pandemic. The entry-point for SARS-CoV-2 is angiotensin converting enzyme 2 (ACE2) and dipeptidyl peptidase 4 (DPP4), which are highly expressed in the lung. Among other complications, COVID-19leads to fatal pneumonia, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) due to development of cytokine storm (CS). The pathogenesis of SARS-CoV-2 infection depends on the viral load and human innate/adaptive immune response that are required for viral elimination in the first phase of COVID-19. However, an exaggerated immune response in the second phase of COVID-19 results in immune overreaction and CS-induced ALI and ARDS. Thus, in view of these considerations, we report here a series of five patients with COVID-19 pneumonia who developed ALI. In addition to the supportive therapy, the patients received doxycycline in the first week and doxycycline plus colchicine in the second week. Following sequential therapy with doxycycline and/or colchicine in patients with COVID-19 pneumonia, the patients had reduction of disease severity and symptoms with better clinical and radiological outcomes. However, it is tough to confirm the link between this therapeutic combination and recovery from COVID-19 pneumonia, as it is a small case-series report. Nevertheless, this study gives a rational for large-scale prospective studies to evaluate the dual sequential effect of doxycycline and colchicine on the COVID-19 severity. This case-series illustrated that use of colchicine: doxycycline combination is linked with marked improvements in the clinical, laboratory and radiological outcomes in patients with COVID-19 pneumonia. However, we cannot sketch any definitive conclusion from our observation, despite we hypothesize that this combination therapeutic regimen may attenuate and treat COVID-19. Further, namely prospective, randomized, and controlled clinical studies are recommended in this regard.