SARS-CoV-2: Repurposed Drugs and Novel Therapeutic Approaches—Insights into Chemical Structure—Biological Activity and Toxicological Screening

Dehelean, Cristina; Lăzureanu, Voichiţa Elena; Coricovac, Dorina; Mioc, Marius; Oancea, Roxana; Marcovici, Iasmina; Pînzaru, Iulia; Şoica, Codruţa; Tsatsakis, Aristidis; Creţu, Octavian

doi:10.3390/jcm9072084

Cited by 44 publications

(59 citation statements)

References 135 publications

(281 reference statements)

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“…Currently, the majority of efforts are focused on curtailing virus spreading, e.g., by blocking its entry into cells, inhibiting its replication, reducing its assembly. Notably, all these approaches are depending on synthetic compounds [ 12 , 13 ]. On the other hand, the blood from convalescent COVID-19 patients which contains naturally occurring antibodies against SARS-CoV-2 has also been used to stop virus invasion and development [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

Tan¹,

Hardeland

2020

Molecules

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Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen’s spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution. Practically, it has a broader protective spectrum than that of only targeting the specific pathogens, which differ in terms of susceptibility. Methods for host targeting applied in one pandemic can even be effective for upcoming pandemics with different pathogens. This is even more urgent if we consider the possible concomitance of two respiratory diseases with potential multi-organ afflictions such as Coronavirus disease 2019 (COVID-19) and seasonal flu. Melatonin is a molecule that can enhance the host’s tolerance against pathogen invasions. Due to its antioxidant, anti-inflammatory, and immunoregulatory activities, melatonin has the capacity to reduce the severity and mortality of deadly virus infections including COVID-19. Melatonin is synthesized and functions in mitochondria, which play a critical role in viral infections. Not surprisingly, melatonin synthesis can become a target of viral strategies that manipulate the mitochondrial status. For example, a viral infection can switch energy metabolism from respiration to widely anaerobic glycolysis even if plenty of oxygen is available (the Warburg effect) when the host cell cannot generate acetyl-coenzyme A, a metabolite required for melatonin biosynthesis. Under some conditions, including aging, gender, predisposed health conditions, already compromised mitochondria, when exposed to further viral challenges, lose their capacity for producing sufficient amounts of melatonin. This leads to a reduced support of mitochondrial functions and makes these individuals more vulnerable to infectious diseases. Thus, the maintenance of mitochondrial function by melatonin supplementation can be expected to generate beneficial effects on the outcome of viral infectious diseases, particularly COVID-19.

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Section: Introductionmentioning

confidence: 99%

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

Tan¹,

Hardeland

2020

Molecules

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“…In addition, there are also other ways to suppress cytokine storms, such as non-steroidal anti-inflammatory medication, immunosuppressants, IFN-λ, corticosteroids, cytokine antagonists, blockers and inhibitors, intravenous immunoglobulin (IVIg), mesenchymal stem cells, sphingosine-1-phosphate receptor 1 agonists, and enabling an increase in vascular permeability (44,56,57). IL-6 is a key factor in immune imbalance, hence it also serves as a target for drugs such as tocilizumab and sarilumab, which are currently on trial (46).…”

Section: Suppression Of Cytokine Storms and Bacterial Infectionsmentioning

confidence: 99%

“…Also, myocardial injury caused by coronavirus infection contributed to poor prognosis (81). At the same time, diabetes or some other comorbidities, and the time span between illness onset and antiviral treatment are major factors influencing the prognosis (57). Age also plays a significant role in prognosis.…”

Section: Prognosismentioning

confidence: 99%

Treatment and prognosis of COVID‑19: Current scenario and prospects (Review)

2020

Exp Ther Med

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SARS-CoV-2 is the seventh member of the family of coronaviruses that can cause infections in humans, termed as COVID-19, which is now a global pandemic. Because it is a novel virus, considerable efforts and extensive studies are needed to fully understand its characteristics. Its symptoms and severity range from mild to critical, depending on several factors, such as host susceptibility to the virus and their immune system, with the most common symptoms being fever, fatigue, sore throat and runny nose. There is no clear treatment available yet, though several options are being explored, with research for vaccines being at the forefront. Traditional Chinese Medicine may also be used as a treatment option. Since this virus is similar to the SARS-CoV and MERS viruses, considerable insight can be gained from previous studies. Although many patients recover completely, there are several factors that lead to poor prognosis. This review summarizes the research carried out so far in terms of treatment options and prognosis factors associated with COVID-19. Contents 1. Introduction 2. Clinical features of COVID-19 3. Current COVID-19 treatment options 4. Prognosis 5. Conclusion

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“…While the number of daily deaths attributable to COVID-19 appears to have decreased substantially by June 2020, the increasing numbers of 'cases' (positive test results for viral exposure) have raised some concerns regarding the ability of governments and decision-making authorities to reduce viral transmission and subsequent consequences ( 2 - 4 ). Currently, at 10 months following the outbreak, no specific treatment for severe forms of COVID-19 has achieved consensus within the medical community, although several potential therapies appear to have produced more or less encouraging results ( 5 - 11 ).…”

Section: Introductionmentioning

confidence: 99%

[Comment] COVID‑19 vaccine safety

Kostoff

Briggs²,

Porter

et al. 2020

Int J Mol Med

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In response to the SARS-coV-2 outbreak, and the resulting cOVId-19 pandemic, a global competition to develop an anti-cOVId-19 vaccine has ensued. The targeted time frame for initial vaccine deployment is late 2020. The present article examines whether short-term, mid-term, and long-term vaccine safety can be achieved under such an accelerated schedule, given the myriad vaccine-induced mechanisms that have demonstrated adverse effects based on previous clinical trials and laboratory research. It presents scientific evidence of potential pitfalls associated with eliminating critical phase II and III clinical trials, and concludes that there is no substitute currently available for long-term human clinical trials to ensure long-term human safety. Vaccine safety testing There are three ways of testing for vaccine safety, in order of increasing credibility: computer simulations, animal experiments and human trials. Computer simulations. While the growth of statistical software packages and chemical descriptors allows the development of new models, safeguards that account for deficiencies of

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SARS-CoV-2: Repurposed Drugs and Novel Therapeutic Approaches—Insights into Chemical Structure—Biological Activity and Toxicological Screening

Cited by 44 publications

References 135 publications

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

Treatment and prognosis of COVID‑19: Current scenario and prospects (Review)

[Comment] COVID‑19 vaccine safety

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