Existing Drugs Considered as Promising in COVID-19 Therapy.
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ABSTRACT:
SUBMITTER: Janik E
PROVIDER: S-EPMC8196765 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 7.1 million people and led to over 0.4 million deaths. Currently, there is no specific anti-SARS-CoV-2 medication. New drug discovery typically takes more than 10 years. Drug repositioning becomes one of the most feasible approaches for combating COVID-19. This work curates the largest available experimental data set for SARS-CoV-2 or SARS-CoV 3CL (main) protease inhibitors. On the basis of this data set, we develop validated machine learning models with relatively low root-mean-square error to screen 1553 FDA-approved drugs as well as another 7012 investigational or off-market drugs in DrugBank. We found that many existing drugs might be potentially potent to SARS-CoV-2. The druggability of many potent SARS-CoV-2 3CL protease inhibitors is analyzed. This work offers a foundation for further experimental studies of COVID-19 drug repositioning.
| S-EPMC7313673 | biostudies-literature
Project description:Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.
| S-EPMC7523486 | biostudies-literature
Project description:The rapid global spread and significant mortality associated with the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection has spurred an urgent race to find effective treatments. Repurposing existing drugs is a particularly attractive approach as pharmacokinetic and safety data already exist; thus, development can leapfrog straight to clinical trials of efficacy, generating results far more quickly than de novo drug development. This review summarizes the state of play for the principle drugs identified as candidates to be repurposed for treating COVID-19 grouped by broad mechanism of action: antiviral, immune enhancing, and antiinflammatory or immunomodulatory. Patient selection, particularly with regard to disease stage, is likely to be key. To date, only dexamethasone and remdesivir have been shown to be effective, but several other promising candidates are in trials.
| S-EPMC7640626 | biostudies-literature
Project description:Intense efforts are underway to evaluate potential therapeutic agents for the treatment of COVID-19. In order to respond quickly to the crisis, the repurposing of existing drugs is the primary pharmacological strategy. Despite the urgent clinical need for these therapies, it is imperative to consider potential safety issues. This is important due to the harm-benefit ratios that may be encountered when treating COVID-19, which can depend on the stage of the disease, when therapy is administered and underlying clinical factors in individual patients. Treatments are currently being trialled for a range of scenarios from prophylaxis (where benefit must greatly exceed risk) to severe life-threatening disease (where a degree of potential risk may be tolerated if it is exceeded by the potential benefit). In this perspective, we have reviewed some of the most widely researched repurposed agents in order to identify potential safety considerations using existing information in the context of COVID-19.
| S-EPMC7404855 | biostudies-literature
Project description:The COVID-19 pandemic has become a priority in the health systems of all nations worldwide. In fact, there are currently no specific drugs or preventive treatments such as vaccines. The numerous therapies available today aim to counteract the symptoms caused by the viral infection that in some subjects can evolve causing acute respiratory distress syndromes (ARDS) with consequent admission to intensive care unit. The exacerbated response of the immune system, through cytokine storm, causes extensive damage to the lung tissue, with the formation of edema, fibrotic tissues and susceptibility to opportunistic infections. The inflammatory picture is also aggravated by disseminated intravascular coagulation which worsens the damage not only to the respiratory system, but also to other organs. In this context, perinatal cells represent a valid strategy thanks to their strong immunomodulatory potential, their safety profile, the ability to reduce fibrosis and stimulate reparative processes. Furthermore, perinatal cells exert antibacterial and antiviral actions. This review therefore provides an overview of the characteristics of perinatal cells with a particular focus on the beneficial effects that they could have in patients with COVID-19, and more specifically for their potential use in the treatment of ARDS and sepsis.
| S-EPMC7841388 | biostudies-literature
Project description:The COVID-19 situation had escalated into an unprecedented global crisis in just a few weeks. On the 30th of January 2020, World Health Organization officially declared the COVID-19 epidemic as a public health emergency of international concern. The confirmed cases were reported to exceed 105,856,046 globally, with the death toll of above 2,311,048, according to the dashboard from Johns Hopkins University on the 7th of February, 2021, though the actual figures may be much higher. Conserved regions of the South Asian strains were used to construct a phylogenetic tree to find evolutionary relationships among the novel virus. Off target similarities were searched with other microorganisms that have been previously reported using Basic Local Alignment Search Tool (BLAST). The conserved regions did not match with any previously reported microorganisms or viruses, which confirmed the novelty of SARS-CoV-2. Currently there is no approved drug for the prevention and treatment of COVID-19, but researchers globally are attempting to come up with one or more soon. Therapeutic strategies need to be addressed urgently to combat COVID-19. Successful drug repurposing is a tool that uses old and safe drugs, is time effective and requires lower development costs, and was thus considered for the study. Molecular docking was used for repurposing drugs from our own comprehensive database of approximately 300 highly characterized, existing drugs with known safety profile, to identify compounds that will inhibit the chosen molecular targets - SARS-CoV-2, ACE2, and TMPRSS2. The study has identified and proposed twenty seven candidates for further in vitro and in vivo studies for the treatment of SARS-CoV-2 infection.
| S-EPMC7906017 | biostudies-literature
Project description:Flavonoids are a class of phenolic natural products, well-identified in traditional and modern medicines in the treatment of several diseases including viral infection. Flavonoids showed potential inhibitory activity against coronaviruses including the current pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and designated as COVID-19. Here, we have collected all data related to the potential inhibitory mechanisms of flavonoids against SARS-CoV-2 infection and their significant immunomodulatory activities. The data were mapped and compared to elect major flavonoids with a promising role in the current pandemic. Further, we have linked the global existence of flavonoids in medicinal plants and their role in protection against COVID-19. Computational analysis predicted that flavonoids can exhibit potential inhibitory activity against SARS-CoV-2 by binding to essential viral targets required in virus entry and/ or replication. Flavonoids also showed excellent immunomodulatory and anti-inflammatory activities including the inhibition of various inflammatory cytokines. Further, flavonoids showed significant ability to reduce the exacerbation of COVID-19 in the case of obesity via promoting lipids metabolism. Moreover, flavonoids exhibit a high safety profile, suitable bioavailability, and no significant adverse effects. For instance, plants rich in flavonoids are globally distributed and can offer great protection from COVID-19. The data described in this study strongly highlighted that flavonoids particularly quercetin and luteolin can exhibit promising multi-target activity against SARS-CoV-2, which promote their use in the current and expected future outbreaks. Therefore, a regimen of flavonoid-rich plants can be recommended to supplement a sufficient amount of flavonoids for the protection and treatment from SARS-CoV-2 infection.
| S-EPMC8139868 | biostudies-literature
Project description:Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. SARS-CoV-2 is an RNA virus and has a glycosylated spike (S) protein used for genome encoding. COVID-19 can lead to a cytokine storm and patients usually have early respiratory signs and further secondary infections, which can be fatal. COVID-19 has entered an emergency phase, but there are still no specific effective drugs for this disease. Mesenchymal stem cells (MSCs) are multipotent stromal cells, which cause antiapoptosis and can repair damaged epithelial cells. Many clinical trials have proved that MSC therapy could be a potential feasible therapy for COVID-19 patients, especially those with acute respiratory distress syndrome, without serious adverse events or toxicities. However, more studies are needed in the future, in order to confirm the effect of this therapy.
| S-EPMC8717529 | biostudies-literature
Project description:While the coronavirus disease 2019 (COVID-19) pandemic advances, the scientific community continues to struggle in the search for treatments. Several improvements have been made, including discovery of the clinical efficacy of chloroquine (CQ) in patients with COVID-19, but effective treatment protocols remain elusive. In the search for novel treatment options, many scientists have used the in-silico approach to identify compounds that could interfere with the key molecules involved in entrance, replication or dissemination of severe acute respiratory syndrome coronavirus-2. However, most of the identified molecules are not available as pharmacological agents at present, and assessment of their safety and efficacy could take many months. This review took a different approach based on the proposed pharmacodynamic model of CQ in COVID-19. The main mechanism of action responsible for the favourable outcome of patients with COVID-19 treated with CQ seems to be related to a pH-modulation-mediated effect on endolysosomal trafficking, a characteristic of chemical compounds often called 'lysosomotropic agents' because of the physico-chemical properties that enable them to diffuse passively through the endosomal membrane and undergo protonation-based trapping in the lumen of the acidic vesicles. This review discusses lysosomotropic and lysosome targeting drugs that are already in clinical use and are characterized by good safety profiles, low cost and wide availability. Some of these drugs -particularly azithromycin and other macrolides, indomethacin and some other non-steroidal anti-inflammatory drugs, proton pump inhibitors and fluoxetine - could provide additional therapeutic benefits in addition to the potential antiviral effect that is still to be confirmed by well-controlled clinical trials. As some of these drugs have probably been used empirically in the treatment of COVID-19, it is hoped that colleagues worldwide will publish patient data to enable evaluation of the potential efficacy of these agents in the clinical context, and rapid implementation in therapeutic protocols if they are shown to have a beneficial effect on clinical outcome.
| S-EPMC7275137 | biostudies-literature
Project description:Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against SARS-CoV-2. Previous studies have shown divergent results regarding protective or damaging immunity induced by prior exposure to sCoVs. It is still unknown whether pre-existing humoral immunity may play a role in the vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera in healthy volunteers before and after immunization with inactivated SARS-CoV-2 vaccines, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level before vaccine immunization, as well as the relationship between pre-existing sCoVs immunity and vaccine-induced neutralization.
2021-10-13 | E-MTAB-11084 | biostudies-arrayexpress