Ivermectin, Famotidine, and Doxycycline: A Suggested Combinatorial Therapeutic for the Treatment of COVID-19

Gupta, Parth Sarthi Sen; Rana, Malay Kumar

doi:10.1021/acsptsci.0c00140

Cited by 21 publications

(23 citation statements)

References 10 publications

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“…IVM is an approved drug for treatment of rosacea due to its antiparasitic properties complemented by anti-inflammatory activity [10][11][12]. In addition, the activity of IVM against various viruses [13], including COVID-19 [14,15], is of a special interest. Several clinical studies are planned or have been started for this indication [16,17].…”

Section: Introductionmentioning

confidence: 99%

Crystal Structures of New Ivermectin Pseudopolymorphs

2021

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New pseudopolymorphs of ivermectin (IVM), a potential anti-COVID-19 drug, were prepared. The crystal structure for three pseudopolymorphic crystalline forms of IVM has been determined using single-crystal X-ray crystallographic analysis. The molecular conformation of IVM in crystals has been compared with the conformation of isolated molecules modeled by DFT calculations. In a solvent with relatively small molecules (ethanol), IVM forms monoclinic crystal structure (space group I2), which contains two types of voids. When crystallized from solvents with larger molecules, like -valerolactone (GVL) and methyl tert-butyl ether (MTBE), IVM forms orthorhombic crystal structure (space group P212121). Calculations of the lattice energy indicate that interactions between IVM and solvents play a minor role; the main contribution to energy is made by the interactions between the molecules of IVM itself, which form a framework in the crystal structure. Interactions between IVM and molecules of solvents were evaluated using Hirshfeld surface analysis. Thermal analysis of the new pseudopolymorphs of IVM was performed by differential scanning calorimetry and thermogravimetric analysis.

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Section: Introductionmentioning

confidence: 99%

Crystal Structures of New Ivermectin Pseudopolymorphs

2021

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“…Alam et al [ 46 ] showed a significant effect of doxycycline and ivermectin combination in the management of mild-to-moderate COVID-19. Similarly, the combination of doxycycline with famotidine is regarded as a robust chemoprophylaxis against COVID-19 [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

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

Al-Kuraishy

Al-Gareeb

Qusty

et al. 2021

Pulmonary Pharmacology & Therapeutics

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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.

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“…Melatonin, such as many other antiparasitic drugs-ivermectin [205][206][207][208][209], doxycycline [210][211][212], metronidazole [213], mefloquine [214], and hydroxychloroquine [215,216]has been suggested as a possible adjuvant agent in the treatment of coronavirus disease 2019 (COVID-19) infection [217][218][219][220][221]. Due to its anti-inflammatory, antioxidant and potent mitoprotective properties, melatonin might be beneficial in the preservation of mitochondrial functions and neuro-and cardioprotection during infections, whereas clarification of its mechanism of action as antiparasitic agent would be an interesting topic for further research.…”

Section: The Role Of Melatonin In the Treatment Of The Protozoan Parasitic Infectionsmentioning

confidence: 99%

Molecular Mechanisms of Melatonin-Mediated Cell Protection and Signaling in Health and Disease

Kopustinskienė

Bernatonienė

2021

Pharmaceutics

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Melatonin, an endogenously synthesized indolamine, is a powerful antioxidant exerting beneficial action in many pathological conditions. Melatonin protects from oxidative stress in ischemic/reperfusion injury, neurodegenerative diseases, and aging, decreases inflammation, modulates the immune system, inhibits proliferation, counteracts the Warburg effect, and promotes apoptosis in various cancer models. Melatonin stimulates antioxidant enzymes in the cells, protects mitochondrial membrane phospholipids, especially cardiolipin, from oxidation thus preserving integrity of the membranes, affects mitochondrial membrane potential, stimulates activity of respiratory chain enzymes, and decreases the opening of mitochondrial permeability transition pore and cytochrome c release. This review will focus on the molecular mechanisms of melatonin effects in the cells during normal and pathological conditions and possible melatonin clinical applications.

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Ivermectin, Famotidine, and Doxycycline: A Suggested Combinatorial Therapeutic for the Treatment of COVID-19

Cited by 21 publications

References 10 publications

Crystal Structures of New Ivermectin Pseudopolymorphs

Crystal Structures of New Ivermectin Pseudopolymorphs

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

Molecular Mechanisms of Melatonin-Mediated Cell Protection and Signaling in Health and Disease

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