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:10.22541/au.158645013.33010796

Cited by 5 publications

(6 citation statements)

References 70 publications

(75 reference statements)

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“…Given the clinical relevance of irADRs and considering that innovative drugs are increasingly authorized by accelerated procedures (Scavone et al, 2017b;Scavone et al, 2017a), further safety investigations in real-life context are necessary (Scavone et al, 2019). We believe that our results could be shared with clinicians that dailies prescribe and administer ICIs or monoclonal antibodies in general.…”

Section: Discussionmentioning

confidence: 76%

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database

et al. 2020

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Background: The introduction of immune checkpoint inhibitors (ICIs) in clinical practice has brought significant benefits for patients. Seven ICIs are available in Europe: nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, cemiplimab, and ipilimumab. Despite their proven clinical efficacy, these innovative drugs may cause serious immune-related adverse drugs reactions (irADRs). Given the significance of these ADRs for patients' health, we analyzed individual case safety reports (ICSRs) related to ICIs, focusing on those reporting irADRs, collected in the Italian spontaneous reporting database. Methods: We analyzed ICI-induced irADRs collected in the Italian Pharmacovigilance database (Rete Nazionale di Farmacovigilanza [RNF]) from January 1, 2002, to February 28, 2019, focusing on those reported in the Campania Region. We retrieved from an open-access Italian pharmacovigilance system, the RAM system (for national safety data), and from the RNF (for Campania safety data) all ICSRs reporting ADRs related to ICIs authorized until the analysis date. Focusing on irADRs, we performed descriptive and disproportionality analyses through the reporting odds ratio (ROR) with 95% confidence interval. Results: National results. Among 2,088 ICI-related ICSRs, 801 reported irADRs. The majority of such ADRs occurred in male patients reporting gastrointestinal and skin toxicities. Nivolumab and pembrolizumab were drugs most commonly reported as suspect drugs. Compared to other ICIs, ROR was statistically significant for pembrolizumab and ipilimumab. Campania Region results. Out of 253 ICI-related ICSRs sent to Regional Pharmacovigilance Center of Campania Region, 121 reported at least one ICI-induced irADR. These were serious in 37.2% of cases and had an unfavorable outcome in 32.2% of cases. Overall, out of 8 ICSRs reported ADR with a fatal outcome, four reported irADRs. From disproportionality analyses on Campania Region ICSRs, statistically significant ROR emerged only for ipilimumab.

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Section: Discussionmentioning

confidence: 76%

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database

et al. 2020

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“…Overall, the results of the current study indicate that a number of potentially useful experimental compounds have promising toxicity profiles, when compared to existing drugs currently being repurposed for Covid-19 treatment, including remdesivir, chloroquine and favipiravir. 9…”

Section: Discussionmentioning

confidence: 99%

“…7 However, the safety and efficacy profiles of these drugs for treating Covid-19 are still being evaluated in clinical trials, and they have been associated with numerous adverse effects, including gastrointestinal abnormalities (such as diarrhoea and vomiting), 8 higher risk of liver impairment and cardiac complications. 9 Another treatment option that is being studied is convalescent plasma therapy, which involves the transfer of convalescent plasma (containing high titres of antibodies against SARS-CoV-2 antigens) from individuals who have recovered from Covid-19 to individuals at high risk (as a prophylactic) or as a means of treatment. Although this therapy has been shown to lead to an improvement in symptoms, the studies performed up to now have involved small sample sizes, and large scale studies are required to establish whether it results in a significant reduction in mortality.…”

Section: Introductionmentioning

confidence: 99%

The Use of In Silico Tools for the Toxicity Prediction of Potential Inhibitors of SARS-CoV-2

Bhat

Chatterjee

2021

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The current strategy for treating the Covid-19 coronavirus disease involves the repurposing of existing drugs or the use of convalescent plasma therapy, as no specific therapeutic intervention has yet received regulatory approval. However, severe adverse effects have been reported for some of these repurposed drugs. Recently, several in silico studies have identified compounds that are potential inhibitors of the main protease (3-chymotrypsin-like cysteine protease) and the nucleocapsid protein of SARS-CoV-2. An essential step of drug development is the careful evaluation of toxicity, which has a range of associated financial, temporal and ethical limitations. In this study, a number of in silico tools were used to predict the toxicity of 19 experimental compounds. A range of web-based servers and applications were used to predict hepatotoxicity, mutagenicity, acute oral toxicity, carcinogenicity, cardiotoxicity, and other potential adverse effects. The compounds were assessed based on the consensus of results, and were labelled as positive or negative for a particular toxicity endpoint. The compounds were then categorised into three classes, according to their predicted toxicity. Ten compounds (52.6%) were predicted to be non-mutagenic and non-hERG inhibitors, and exhibited zero or low level hepatotoxicity and carcinogenicity. Furthermore, from the consensus of results, all 19 compounds were predicted to be non-mutagenic and negative for acute oral toxicity. Overall, most of the compounds displayed encouraging toxicity profiles. These results can assist further lead optimisation studies and drug development efforts to combat Covid-19.

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“…However, current management is supportive, and without specific antivirus drugs or vaccine against COVID‐19. [ 1 ] While the pathogenesis of COVID‐19 remains elusive, accumulating evidence suggests that a subgroup of patients with severe COVID‐19 might have cytokine storm syndrome. [ 2,3 ] Cytokine storm is a serious immune dysregulation resultant from overproduction of cytokines, which often occurs during virus infection, [ 4 ] organ transplant, [ 5 ] immunotherapy, [ 6 ] and autoimmune diseases, [ 7 ] and may result in death if untreated.…”

Section: Methodsmentioning

confidence: 99%

An Antioxidant Enzyme Therapeutic for COVID‐19

et al. 2020

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The COVID‐19 pandemic has taken a significant toll on people worldwide, and there are currently no specific antivirus drugs or vaccines. Herein it is a therapeutic based on catalase, an antioxidant enzyme that can effectively breakdown hydrogen peroxide and minimize the downstream reactive oxygen species, which are excessively produced resulting from the infection and inflammatory process, is reported. Catalase assists to regulate production of cytokines, protect oxidative injury, and repress replication of SARS‐CoV‐2, as demonstrated in human leukocytes and alveolar epithelial cells, and rhesus macaques, without noticeable toxicity. Such a therapeutic can be readily manufactured at low cost as a potential treatment for COVID‐19.

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Current pharmacological treatments for COVID-19: what’s next?

Abstract: This a preprint and has not been peer reviewed. Data may be preliminary.

Cited by 5 publications

References 70 publications

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database

The Use of In Silico Tools for the Toxicity Prediction of Potential Inhibitors of SARS-CoV-2

An Antioxidant Enzyme Therapeutic for COVID‐19

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