Abstract:COVID-19 has recently grown to be pandemic all around the world. Therefore, efforts to find effective drugs for the treatment of COVID-19 are needed to improve humans’ life quality and survival. Since the main protease (M
pro
) of SARS-CoV-2 plays a crucial role in viral replication and transcription, the inhibition of this enzyme could be a promising and challenging therapeutic target to fight COVID-19. The present study aims to identify alkaloid compounds as new potential inhibitors fo… Show more
“…Additionally, almitrine is frequently used in conjunction with another drug called raubasine, which acts as a vasodilator, for the treatment of age-related cerebral disorders ( Allain and Bentué-Ferrer, 1998 ) and certain pulmonary diseases. Notably, raubasine has demonstrated anti-SARS-CoV-2 effects in in vitro and animal studies, suggesting its therapeutic potential ( Kumar et al, 2021 ; Mohseni et al, 2022 ).…”
Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, a large number of critically ill and severe COVID-19 patients meet the diagnostic criteria for sepsis and even septic shock. The treatments for COVID-19 patients with sepsis are still very limited. For sepsis, improving ventilation is one of the main treatments. Nitric oxide (NO) and almitrine have been reported to improve oxygenation in patients with “classical” sepsis. Here, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of NO, almitrine, and the combination of both for COVID-19 (at the edge of sepsis) patients.Method: A systematic search was performed on Embase, PubMed, the Cochrane Library, the Web of Science, Wanfang Data, and China National Knowledge Infrastructure. Randomized clinical trials, cohort studies, cross-sectional studies, case-control studies, case series, and case reports in COVID-19 patients with suspected or confirmed sepsis were performed. Study characteristics, patient demographics, interventions, and outcomes were extracted from eligible articles.Results: A total of 35 studies representing 1,701 patients met eligibility criteria. Inhaled NO did not affect the mortality (OR 0.96, 95% CI 0.33–2.8, I2 = 81%, very low certainty), hospital length of stay (SMD 0.62, 95% CI 0.04–1.17, I2 = 83%, very low certainty), and intubation needs (OR 0.82, 95% CI 0.34–1.93, I2 = 56%, very low certainty) of patients with COVID-19 (at the edge of sepsis). Meanwhile, almitrine did not affect the mortality (OR 0.44, 95% CI 0.17–1.13, low certainty), hospital length of stay (SMD 0.00, 95% CI -0.29–0.29, low certainty), intubation needs (OR 0.94, 95% CI 0.5–1.79, low certainty), and SAEs (OR 1.16, 95% CI 0.63–2.15, low certainty). Compared with pre-administration, the PaO2/FiO2 of patients with NO (SMD-0.87, 95% CI -1.08–0.66, I2 = 0%, very low certainty), almitrine (SMD-0.73, 95% CI-1.06–0.4, I2 = 1%, very low certainty), and the combination of both (SMD-0.94, 95% CI-1.71–0.16, I2 = 47%, very low certainty) increased significantly.Conclusion: Inhaled NO, almitrine, and the combination of the two drugs improved oxygenation significantly, but did not affect the patients’ mortality, hospitalization duration, and intubation needs. Almitrine did not significantly increase the patients’ SAEs. Well-designed high-quality studies are needed for establishing a stronger quality of evidence.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367667, identifier CRD42022367667.
“…Additionally, almitrine is frequently used in conjunction with another drug called raubasine, which acts as a vasodilator, for the treatment of age-related cerebral disorders ( Allain and Bentué-Ferrer, 1998 ) and certain pulmonary diseases. Notably, raubasine has demonstrated anti-SARS-CoV-2 effects in in vitro and animal studies, suggesting its therapeutic potential ( Kumar et al, 2021 ; Mohseni et al, 2022 ).…”
Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, a large number of critically ill and severe COVID-19 patients meet the diagnostic criteria for sepsis and even septic shock. The treatments for COVID-19 patients with sepsis are still very limited. For sepsis, improving ventilation is one of the main treatments. Nitric oxide (NO) and almitrine have been reported to improve oxygenation in patients with “classical” sepsis. Here, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of NO, almitrine, and the combination of both for COVID-19 (at the edge of sepsis) patients.Method: A systematic search was performed on Embase, PubMed, the Cochrane Library, the Web of Science, Wanfang Data, and China National Knowledge Infrastructure. Randomized clinical trials, cohort studies, cross-sectional studies, case-control studies, case series, and case reports in COVID-19 patients with suspected or confirmed sepsis were performed. Study characteristics, patient demographics, interventions, and outcomes were extracted from eligible articles.Results: A total of 35 studies representing 1,701 patients met eligibility criteria. Inhaled NO did not affect the mortality (OR 0.96, 95% CI 0.33–2.8, I2 = 81%, very low certainty), hospital length of stay (SMD 0.62, 95% CI 0.04–1.17, I2 = 83%, very low certainty), and intubation needs (OR 0.82, 95% CI 0.34–1.93, I2 = 56%, very low certainty) of patients with COVID-19 (at the edge of sepsis). Meanwhile, almitrine did not affect the mortality (OR 0.44, 95% CI 0.17–1.13, low certainty), hospital length of stay (SMD 0.00, 95% CI -0.29–0.29, low certainty), intubation needs (OR 0.94, 95% CI 0.5–1.79, low certainty), and SAEs (OR 1.16, 95% CI 0.63–2.15, low certainty). Compared with pre-administration, the PaO2/FiO2 of patients with NO (SMD-0.87, 95% CI -1.08–0.66, I2 = 0%, very low certainty), almitrine (SMD-0.73, 95% CI-1.06–0.4, I2 = 1%, very low certainty), and the combination of both (SMD-0.94, 95% CI-1.71–0.16, I2 = 47%, very low certainty) increased significantly.Conclusion: Inhaled NO, almitrine, and the combination of the two drugs improved oxygenation significantly, but did not affect the patients’ mortality, hospitalization duration, and intubation needs. Almitrine did not significantly increase the patients’ SAEs. Well-designed high-quality studies are needed for establishing a stronger quality of evidence.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367667, identifier CRD42022367667.
“…SARS-CoV-2 (Main Protease, M pro ) Inhibitor SARS-CoV-2 main protease (M pro or 3CL pro ) controls many essential viral processes including maturation, replication, and transcription. This makes it a potential target for optimizing therapeutics against COVID-19 [154,155]. Paxlovid is a prominent protease inhibitor approved by the FDA at the end of 2021 for mild and moderately effected patients.…”
Section: In Silico Predicted Anti-sars-cov-2 Indolesmentioning
The COVID-19 pandemic has posed a significant threat to society in recent times, endangering human health, life, and economic well-being. The disease quickly spreads due to the highly infectious SARS-CoV-2 virus, which has undergone numerous mutations. Despite intense research efforts by the scientific community since its emergence in 2019, no effective therapeutics have been discovered yet. While some repurposed drugs have been used to control the global outbreak and save lives, none have proven universally effective, particularly for severely infected patients. Although the spread of the disease is generally under control, anti-SARS-CoV-2 agents are still needed to combat current and future infections. This study reviews some of the most promising repurposed drugs containing indolyl heterocycle, which is an essential scaffold of many alkaloids with diverse bio-properties in various biological fields. The study also discusses natural and synthetic indole-containing compounds with anti-SARS-CoV-2 properties and computer-aided drug design (in silico studies) for optimizing anti-SARS-CoV-2 hits/leads.
“…Coronavirus main protease (M pro , also called 3CL pro ) plays an essential role in viral maturation, replication and transcription. Thus, the inhibition of M pro is an attractive target for therapeutics against COVID-19 [ 15 , 16 ]. By the end of 2021, FDA (Food and Drug Administration) approved (under the emergency use authorization) Paxlovid as anti-SARS-CoV-2 therapeutic for mild and moderate COVID-19 patients.…”
Section: Introductionmentioning
confidence: 99%
“…2-Substituted indolealkylamines were mentioned as potential anti-SARS-CoV-2 candidates with viral main protease (M pro ) inhibitory properties [ 21 ]. Many indole-containing compounds have also been mentioned by the in-silico studies as M pro inhibitory properties but lack of experimental bio-evidence has hindered their applicability [ 15 , [22] , [23] , [24] , [25] ]. Fig.…”
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