Combining immunomodulators and antivirals for COVID-19.
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ABSTRACT:
SUBMITTER: Chen LYC
PROVIDER: S-EPMC8172169 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The majority of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals remain paucisymptomatic, contrasting with a minority of infected individuals in danger of death. Here, we speculate that the robust disease resistance of most individuals is due to a swift production of type I interferon (IFNα/β), presumably sufficient to lower the viremia. A minority of infected individuals with a preexisting chronic inflammatory state fail to mount this early efficient response, leading to a delayed harmful inflammatory response. To improve the epidemiological scenario, we propose combining: (i) the development of efficient antivirals administered early enough to assist in the production of endogenous IFNα/β; (ii) potentiating early IFN responses; (iii) administering anti-inflammatory treatments when needed, but not too early to interfere with endogenous antiviral responses.
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Project description:Inflammation plays a crucial role in COVID-19, and when it becomes dysregulated, it can lead to severe outcomes, including death. Naphthoquinones, a class of cyclic organic compounds widely distributed in nature, have attracted significant interest due to their potential biological benefits. One such naphthoquinone is 3,5,8-trihydroxy-6-methoxy-2-(5-oxohexa-1,3-dienyl)-naphthanthene-1,4-dione (3,5,8-TMON), a compound produced by fungi. Despite its structural similarity to shikonin, limited research has been conducted to investigate its biological properties. Therefore, the objective of this study was to evaluate the effects of 3,5,8-TMON and its synthetic derivatives in the context of inflammation induced by lipopolysaccharide (LPS) and SARS-CoV-2 infection in vitro using cell cultures. 3,5,8-TMON was obtained by acid treatment of crude extracts of fermentation medium from Cordyceps sp., and two derivatives were accessed by reaction with phenylhydrazine under different conditions. The results revealed that the crude extract of the fungi (C. Ex) inhibited the activity of transcription factor NF-kB, as well as the production of nitric oxide (NO) and interleukin-6 (IL-6) when LPS induced it in RAW 264.7 cells. This inhibitory effect was observed at effective concentrations of 12.5 and 3.12 μg mL-1. In parallel, 3,5,8-TMON and the new derivatives 3 and 4 demonstrated the ability to decrease IL-6 production while increasing TNF, with a specific effect depending on the concentration. These concentration-dependent agonist and antagonist effects were observed in THP-1 cells. Furthermore, 3,5,8-TMON inhibited IL-6 production at concentrations of 12.5 and 3.12 μg mL-1 in Calu-3 cells during SARS-CoV-2 viral infection. These findings present promising opportunities for further research into the therapeutic potential of this class of naphthoquinone in the management of inflammation and viral infections.
| S-EPMC10880745 | biostudies-literature
Project description:Throughout history, disease outbreaks have worked havoc upon humanity, sometimes reorienting the history and at times, signaling the end of entire civilizations and the modern pandemic that the world is dealing with, is COVID-19 or SARS-CoV-2. A healthy immunity could be an ideal gear for resisting COVID-19 for neither medicines nor vaccines have been ascertained till date. In view of the present scenario, there is a demanding necessity to analyze innovative and valid techniques for forestalling and cure of COVID-19 by re-evaluating the structure of the natural compounds for drug designing. The Ayurveda has come forward by prescribing a lot of medicinal herbs for combating this dreaded disease. We have searched from sources in Pubmed and Google Scholar and found 1509 items. The search criteria were limited to the effect of phytochemicals in certain immunomodulatory aspects of viral infection. The original research papers related to the works on phytochemicals in the down regulation of NF-kB, activation of NK and CD8+ cells, inhibition of inflammatory cytokine release and ROS scavenging were included in our study. Here, we try to focus on the immunoregulatory cells which have a vital aspect in COVID-19 and highlight the potential effects of the restorative use of phytochemicals as drugs or dietary supplements.Supplementary informationThe online version contains supplementary material available at 10.1007/s13337-021-00706-2.
| S-EPMC8224255 | biostudies-literature
Project description:The emergency state caused by COVID-19 saw the use of immunomodulators despite the absence of robust research. To date, the results of relatively few randomized controlled trials have been published, and methodological approaches are riddled with bias and heterogeneity. Anti-SARS-CoV-2 antibodies, convalescent plasma and the JAK inhibitor baricitinib have gained Emergency Use Authorizations and tentative recommendations for their use in clinical practice alone or in combination with other therapies. Anti-SARS-CoV-2 antibodies are predominating the management of non-hospitalized patients, while the inpatient setting is seeing the use of convalescent plasma, baricitinib, tofacitinib, tocilizumab, sarilumab, and corticosteroids, as applicable. Available clinical data also suggest the potential clinical benefit of the early administration of blood-derived products (e.g. convalescent plasma, non-SARS-CoV-2-specific immunoglobins) and the blockade of factors implicated in the hyperinflammatory state of severe COVID-19 (Interleukin 1 and 6; Janus Kinase). Immune therapies seem to have a protective effect and using immunomodulators alone or in combination with viral replication inhibitors and other treatment modalities might prevent progression into severe COVID-19 disease, cytokine storm and death. Future trials should address existing gaps and reshape the landscape of COVID-19 management.
| S-EPMC8862162 | biostudies-literature
Project description:The coronavirus disease of 2019 (COVID-19) has caused an unprecedented global crisis. The etiological agent is a new virus called the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). As of October, 2020 there have been 45.4 million confirmed cases with a mortality rate of 2.6% globally. With the lack of a vaccine and effective treatments, the race is on to find a cure for the virus infection using specific antivirals. The viral RNA-dependent RNA polymerase, proteases, spike protein-host angiotensin-converting enzyme 2 binding and fusion have presented as attractive targets for pan-coronavirus and broad spectrum direct-acting antivirals (DAAs). This review presents a perspective on current re-purposing treatments and future DAAs.
| S-EPMC7688518 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) is an infective disease generated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the pandemic urgency and lack of an effective cure for this disease, drug repurposing could open the way for finding a solution. Lots of investigations are ongoing to test the compounds already identified as antivirals. On the other hand, induction of type I interferons are found to play an important role in the generation of immune responses against SARS-CoV-2. Therefore, it was opined that the antivirals capable of triggering the interferons and their signaling pathway, could rationally be beneficial for treating COVID-19. On this basis, using a database of antivirals, called drugvirus, some antiviral agents were derived, followed by searches on their relevance to interferon induction. The examined list included drugs from different categories such as antibiotics, immunosuppressants, anti-cancers, non-steroidal anti-inflammatory drugs (NSAID), calcium channel blocker compounds, and some others. The results as briefed here, could help in finding potential drug candidates for COVID-19 treatment. However, their advantages and risks should be taken into account through precise studies, considering a systemic approach. Even though the adverse effects of some of these drugs may overweight their benefits, considering their mechanisms and structures may give a clue for designing novel drugs in the future. Furthermore, the antiviral effect and IFN-modifying mechanisms possessed by some of these drugs might lead to a synergistic effect against SARS-CoV-2, which deserve to be evaluated in further investigations.
| S-EPMC7705326 | biostudies-literature
Project description: Not available
| S-EPMC8651252 | biostudies-literature
Project description:BackgroundAntivirals have been given widely for patients with COVID-19 breakthrough in Asian countries, creating a "black market" for unapproved and unprescribed medications. More evidence is needed to clarify the benefits of antivirals in these settings.MethodsWe conducted a random-sampling retrospective cohort study at a general hospital in Vietnam. We recruited patients with mild-to-moderate COVID-19 breakthrough who were given either standard of care (SoC) alone or SoC + antiviral. Primary outcome was residual respiratory symptoms that lasted > 7 days. Secondary outcome was long COVID-19, diagnosed by specialized physicians. We used logistic regression to measure odds ratio (OR), in addition to a sensitivity and subgroup analyses to further explore the results.ResultsA total of 142 patients (mean age 36.2 ± 9.8) were followed. We recorded residual symptoms in 27.9% and 20.3% of the SoC and SoC + antiviral group, while the figures for long COVID-19 were 11.8% and 8.1%, respectively. Antiviral use was not significantly associated with lower the risks of residual symptoms (OR = 0.51, 95% CI: 0.22-1.20, p = 0.12) or long COVID-19 (OR = 0.55, 95% CI: 0.16-1.90, p = 0.35). The sensitivity and subgroup analyses did not show any significant differences between the study groups (all p > 0.05).ConclusionAntivirals were not associated with faster resolution of respiratory symptoms or lower risks of long COVID-19. Further studies should focus on different antivirals to confirm their effects on different sub-populations. Meanwhile, antivirals should only be used in very high-risk patients to avoid excessive costs and harms.
| S-EPMC10763260 | biostudies-literature
Project description: Not available
| S-BSST563 | biostudies-other