Current pharmacological treatments for COVID‐19: What's next?

Scavone, Cristina; Brusco, Simona; Bertini, Michele; Sportiello, Liberata; Rafaniello, Concetta; Zoccoli, Alice; Berrino, Liberato; Racagni, Giorgio; Rossi, Francesco; Capuano, Annalisa

doi:10.1111/bph.15072

Cited by 250 publications

(234 citation statements)

References 92 publications

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“… Could interfere the interaction of the virus with the host cell entry receptors to prevent their cellular endocytosis, replication and infection. Can protect the vital and target organs by executing the anti-inflammatory activity against cytokine storm induced organ damage, as anti-inflammatory activity of the natural herbs or Phytocompounds may confer the vasodilation of bronchial tube ( Ignarro, 2020 ; Scavone et al ., 2020 ). …”

Section: Resultsmentioning

confidence: 99%

Phytopharmaceuticals mediated Furin and TMPRSS2 receptor blocking: can it be a potential therapeutic option for Covid-19?

et al. 2021

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Currently, novel coronavirus disease (Covid-19) outbreak creates global panic across the continents, as people from almost all countries and territories have been affected by this highly contagious viral disease. The scenario is deteriorating due to lack of proper & specific target-oriented pharmacologically safe prophylactic agents or drugs, and or any effective vaccine. drug development is urgently required to back in the normalcy in the community and to combat this pandemic. Thus, we have proposed two novel drug targets, Furin and TMPRSS2, as Covid-19 treatment strategy. We have highlighted this target-oriented novel drug delivery strategy, based on their pathophysiological implication on SARS-CoV-2 infection, as evident from earlier SARS-CoV-1, MERS, and influenza virus infection via host cell entry, priming, fusion, and endocytosis. An earlier study suggested that Furin and TMPRSS2 knockout mice had reduced level of viral load and a lower degree of organ damage such as the lung. The present study thus highlights the promise of some selected novel and potential anti-viral Phytopharmaceutical that bind to Furin and TMPRSS2 as target. As, few of them had shown promising anti-viral response in both preclinical and clinical study with acceptable therapeutic safety-index. Hence, this strategy may limit life-threatening Covid-19 infection and its mortality rate through nano-suspension based intra-nasal or oral nebulizer spray, to treat mild to moderate SARS-COV-2 infection, when Furin and TMPRSS2 receptor may initiate to express and activate for processing the virus to cause cellular infection by replication within the host cell.

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Section: Resultsmentioning

confidence: 99%

Phytopharmaceuticals mediated Furin and TMPRSS2 receptor blocking: can it be a potential therapeutic option for Covid-19?

et al. 2021

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“…These include antiviral, immunomodulatory, anti-inflammatory and miscellaneous drugs. A comprehensive review of the current status of these trials has been published [ 47 ] and examples of these therapies will be discussed briefly here, in particular, Remdesivir, the antimalarial drugs chloroquine and hydroxychloroquine, glucocorticoids, IFN-β, IL-6 antagonists and angiotensin-converting enzyme 2 (ACE 2) inhibitors.…”

Section: Potential Therapies Of Covid-19mentioning

confidence: 99%

Immunotherapy of COVID-19 with poly (ADP-ribose) polymerase inhibitors: starting with nicotinamide

Badawy

2020

Bioscience Reports

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COVID-19 induces a proinflammatory environment that is stronger in patients requiring intensive care. The cytokine components of this environment may determine efficacy or otherwise of glucocorticoid therapy. The immunity modulators, the aryl hydrocarbon receptor (AhR) and the nuclear NAD+-consuming enzyme poly (ADP-ribose) polymerase 1 (PARP 1) may play a critical role in COVID-19 pathophysiology. The AhR is over-expressed in coronaviruses, including COVID-19 and, as it regulates PARP gene expression, the latter is likely to be activated in COVID-19. PARP 1 activation leads to cell death mainly by depletion of NAD+ and ATP, especially when availability of these energy mediators is compromised. PARP expression is enhanced in other lung conditions: the pneumovirus respiratory syncytial virus (RSV) and chronic obstructive pulmonary disease (COPD). I propose that PARP 1 activation is the terminal point in a sequence of events culminating in patient mortality and should be the focus of COVID-19 immunotherapy. Potent PARP 1 inhibitors are undergoing trials in cancer, but a readily available inhibitor, nicotinamide, which possesses a highly desirable biochemical and activity profile, merits exploration. It conserves NAD+ and prevents ATP depletion by PARP 1 and Sirtuin 1 inhibition, enhances NAD+ synthesis, and hence that of NADP+ which is a stronger PARP inhibitor, reverses lung injury caused by ischaemia/reperfusion, inhibits proinflammatory cytokines, and is effective against HIV infection. These properties qualify nicotinamide for therapeutic use initially in conjunction with standard clinical care or combined with other agents, and subsequently as an adjunct to stronger PARP 1 inhibitors or other drugs.

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“…Tocilizumab, an anti-interleukin 6 receptor antibody, has been used in small studies with early reports of success. A dose of 400 mg was associated with clinical improvements and successful discharge, with most patients only receiving a single dose [29,30]. Several randomized clinical trials on tocilizumab, either alone or in combination, in patients with COVID-19 with severe pneumonia are underway, and its use was included in the Chinese national treatment guidelines [30,31].…”

Section: Discussionmentioning

confidence: 99%

Differences between Clinical Protocols for the Treatment of Coronavirus Disease 2019 (COVID-19) in Andalusia, Spain

Pérez‐Belmonte

López-Carmona

Quevedo-Marín

et al. 2020

IJERPH

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Our objective was to compare clinical protocols for the treatment of the novel coronavirus disease 2019 (COVID-19) among different hospitals in Andalusia, Spain. We reviewed the current COVID-19 protocols of the 15 largest hospitals in Andalusia. Antiviral treatment, empirical antibacterial agents, adjunctive therapies, anticoagulant treatment, supportive care, hospital organization, and discharge recommendations were analyzed. All protocols included were the latest updates as of July 2020. Hydroxychloroquine in monotherapy was the most frequent antiviral drug recommended for mild respiratory illness with clinical risk factors (33.3%). Combined hydroxychloroquine with azithromycin or lopinavir/ritonavir was found in 40% of protocols. The recommended treatment for patients with mild and moderate pneumonias was different antiviral combinations including hydroxychloroquine plus azithromycin (93.3%) or hydroxychloroquine plus lopinavir/ritonavir (79.9%). Different combinations of hydroxychloroquine and lopinavir/ritonavir (46.7%) and triple therapy with hydroxychloroquine, azithromycin, and lopinavir/ritonavir (40%) were the most recommended treatments for patients with severe pneumonia. There were five corticosteroid regimens, which used dexamethasone, methylprednisolone, or prednisone, with different doses and treatment durations. Anakinra was included in seven protocols with six different regimens. All protocols included prophylactic heparin and therapeutic doses for thromboembolism. Higher prophylactic doses of heparin for high-risk patients and therapeutic doses for patients in critical condition were included in 53.3% and 33.3% of protocols, respectively. This study showed that COVID-19 protocols varied widely in several aspects (antiviral treatment, corticosteroids, anakinra, and anticoagulation for high risk of thrombosis or critical situation). Rigorous randomized clinical trials on the proposed treatments are needed to provide consistent evidence.

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Current pharmacological treatments for COVID‐19: What's next?

Cited by 250 publications

References 92 publications

Phytopharmaceuticals mediated Furin and TMPRSS2 receptor blocking: can it be a potential therapeutic option for Covid-19?

Phytopharmaceuticals mediated Furin and TMPRSS2 receptor blocking: can it be a potential therapeutic option for Covid-19?

Immunotherapy of COVID-19 with poly (ADP-ribose) polymerase inhibitors: starting with nicotinamide

Differences between Clinical Protocols for the Treatment of Coronavirus Disease 2019 (COVID-19) in Andalusia, Spain

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