Repurposing existing drugs for the treatment of COVID-19/SARS-CoV-2 infection: A review describing drug mechanisms of action

Yousefi, Hassan; Mashouri, Ladan; Okpechi, Samuel C.; Alahari, Nikhilesh V.; Alahari, Suresh K.

doi:10.1016/j.bcp.2020.114296

Cited by 93 publications

(84 citation statements)

References 216 publications

(188 reference statements)

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“…To treat COVID-19, most countries have, in emergency, approved the usage of several antiviral drugs, and physicians have been using all sorts of drugs and oxygen supplementation to save the lives of COVID-19 patients. Most of these drugs, especially antiviral drugs, have been repurposed for treatment against COVID-19, as no anti-SARS-CoV-2 drug has been developed yet [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Repurposing NASVAC, a hepatitis B therapeutic vaccine, for pre- and postexposure prophylaxis of SARS-CoV-2 infection

Akbar

Mahtab

Aguilar

et al. 2021

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent coronavirus 2019 (COVID-19) have led to tens of millions of cases and millions of deaths around the world. Although more than a year has passed since the emergence of COVID-19, more waves of the pandemic, with new variants of the deadly virus, have been reported. It seems that the virus will continue to infect people for years or decades to come and thus lead to more illnesses and deaths. The experiences last year regarding limiting the transmission of the virus indicate that one or more traditional methods of containment may not be effective; further, even vaccination may not give immunity to society. On the other hand, eliminating the virus using drugs capable of eradicating SARS-CoV-2 from the infected host may not be an achievable goal. Based on these realities and after exploring the mechanism underlying the acquisition of the virus and pathogenesis of COVID-19, we assumed that immune therapy may be a practical option for the containment of SARS-CoV-2. In this study, we repurposed an immune modulator containing two antigens of hepatitis B virus, hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) (termed NASVAC, Center for Genetic Engineering and Biotechnology, CIGB, Havana, Cuba), to gain insight into its role against SARS-CoV-2. NASVAC induced cytokines of innate immunity following nasal administration and prevented all 20 volunteers from being diagnosed with SARS-CoV-2 during the two weeks of usage. Four volunteers were infected with SARS-CoV-2 two weeks after the end of NASVAC administration; three of them showed almost no symptoms and recovered without any intervention, and one with several comorbidities attended a hospital for four days and recovered completely. In conclusion, the administration of NASVAC to subjects at risk of SARS-CoV-2 infection was safe. The pattern of cytokine responses and absence of infection or mild COVID-19 infection of the subjects involved in the study are preliminary evidence indicating that this product may prevent or suppress SARS-CoV-2 infection at the initial stages of SARS-CoV-2 acquisition and/or replication and deserve further exploratory trials to confirm the capacity of NASVAC as pre/postexposure prophylaxis or pre-emptive therapy in the context of SARS-CoV-2 infection.

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Section: Introductionmentioning

confidence: 99%

Repurposing NASVAC, a hepatitis B therapeutic vaccine, for pre- and postexposure prophylaxis of SARS-CoV-2 infection

Akbar

Mahtab

Aguilar

et al. 2021

Preprint

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“…As a popular example of broad-spectrum antiviral activities, remdesivir inhibits many RNA viruses such as ebolavirus and respiratory pathogens including Middle East respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2 [ 70 ]. In regards to the worldwide spread of COVID-19 [ 71 , 72 , 73 ], the US FDA approved remdesivir (Veklury ® )—a monophosphoramidate prodrug of an adenosine analogue ( Figure 1 e) that acts as a direct-acting antiviral to treat COVID-19 [ 74 ]. Remdesivir, unlike other N-nucleoside analogues from Figure 1 , Figure 2 , Figure 3 , Figure 4 and Figure 5 , is a C-nucleoside analogue that is stably resistant against phosphorolytic degradation caused by phosphorylases [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Drug Discovery of Nucleos(t)ide Antiviral Agents: Dedicated to Prof. Dr. Erik De Clercq on Occasion of His 80th Birthday

Yue

Zhang

et al. 2021

Molecules

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Nucleoside and nucleotide analogues are essential antivirals in the treatment of infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). To celebrate the 80th birthday of Prof. Dr. Erik De Clercq on 28 March 2021, this review provides an overview of his contributions to eight approved nucleos(t)ide drugs: (i) three adenosine nucleotide analogues, namely tenofovir disoproxil fumarate (Viread®) and tenofovir alafenamide (Vemlidy®) against HIV and HBV infections and adefovir dipivoxil (Hepsera®) against HBV infections; (ii) two thymidine nucleoside analogues, namely brivudine (Zostex®) against HSV-1 and VZV infections and stavudine (Zerit®) against HIV infections; (iii) two guanosine analogues, namely valacyclovir (Valtrex®, Zelitrex®) against HSV and VZV and rabacfosadine (Tanovea®-CA1) for the treatment of lymphoma in dogs; and (iv) one cytidine nucleotide analogue, namely cidofovir (Vistide®) for the treatment of HCMV retinitis in AIDS patients. Although adefovir dipivoxil, stavudine, and cidofovir are virtually discontinued for clinical use, tenofovir disoproxil fumarate and tenofovir alafenamide remain the most important antivirals against HIV and HBV infections worldwide. Overall, the broad-spectrum antiviral potential of nucleos(t)ide analogues supports their development to treat or prevent current and emerging infectious diseases worldwide.

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“…The IL-6 receptor antagonist tocilizumab has been used in some cases of severe COVID-19 [ 86 , 87 , 88 , 89 , 90 ]. However, the benefits of tocilizumab for the treatment of COVID-19 are uncertain, [ 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ] and the Italian Medicines Agency (AIFA) announced on June 18, 2020 that tocilizumab (Actemra) did not improve COVID-19 outcomes [ 91 , 92 , 93 ]. However, a recent meta-analysis reported a reduced mortality prevalence in patients treated with tocilizumab [ 97 ].…”

Section: Diabesity Meta-inflammation and Il-6: The Role In Severmentioning

confidence: 99%

“…However, a recent meta-analysis reported a reduced mortality prevalence in patients treated with tocilizumab [ 97 ]. Sarilumab is another IL-6 receptor antagonist under investigation in clinical trials [ 91 , 98 , 99 ]. In addition to IL-6 receptor targeting, clinical trials with anti-IL-6 treatments (clazakizumab and siltuximabin) are ongoing [ 99 ].…”

Section: Diabesity Meta-inflammation and Il-6: The Role In Severmentioning

confidence: 99%

Mediterranean Diet for the Prevention of Gestational Diabetes in the Covid-19 Era: Implications of Il-6 In Diabesity

Fedullo¹,

Schiattarella

Morlando

et al. 2021

IJMS

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The aim of this review is to highlight the influence of the Mediterranean Diet (MedDiet) on Gestational Diabetes Mellitus (GDM) and Gestational Weight Gain (GWG) during the COVID-19 pandemic era and the specific role of interleukin (IL)-6 in diabesity. It is known that diabetes, high body mass index, high glycated hemoglobin and raised serum IL-6 levels are predictive of poor outcomes in coronavirus disease 2019 (COVID-19). The immunopathological mechanisms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection include rising levels of several cytokines and in particular IL-6. The latter is associated with hyperglycemia and insulin resistance and could be useful for predicting the development of GDM. Rich in omega-3 polyunsaturated fatty acids, vitamins, and minerals, MedDiet improves the immune system and could modulate IL-6, C reactive protein and Nuclear Factor (NF)-κB. Moreover, polyphenols could modulate microbiota composition, inhibit the NF-κB pathway, lower IL-6, and upregulate antioxidant enzymes. Finally, adhering to the MedDiet prior to and during pregnancy could have a protective effect, reducing GWG and the risk of GDM, as well as improving the immune response to viral infections such as COVID-19.

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Repurposing existing drugs for the treatment of COVID-19/SARS-CoV-2 infection: A review describing drug mechanisms of action

Abstract: Graphical abstract

Cited by 93 publications

References 216 publications

Repurposing NASVAC, a hepatitis B therapeutic vaccine, for pre- and postexposure prophylaxis of SARS-CoV-2 infection

Repurposing NASVAC, a hepatitis B therapeutic vaccine, for pre- and postexposure prophylaxis of SARS-CoV-2 infection

Drug Discovery of Nucleos(t)ide Antiviral Agents: Dedicated to Prof. Dr. Erik De Clercq on Occasion of His 80th Birthday

Mediterranean Diet for the Prevention of Gestational Diabetes in the Covid-19 Era: Implications of Il-6 In Diabesity

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