The Current Recommended Drugs and Strategies for the Treatment of Coronavirus Disease (COVID-19)

Abstract

Background: The coronavirus 2019 (COVID-19) has been known as a pandemic disease by the World Health Organization (WHO) worldwide. The drugs currently used for treatment of COVID-19 are often selected and tested based on their effectiveness in other diseases such as influenza and AIDS and their major identified targets are viral protease, host cell produced protease, viral RNA polymerase, and the interaction site of viral protein with host cell receptors. Until now, there are no approved therapeutic drugs for definitive treatment of this dangerous disease.

Methods: In this article, all of the documentary information, such as clinical trials, original research and reviews, government's database, and treatment guidelines, were reviewed critically and comprehensively. Moreover, it was attempted to present the most common and effective drugs and strategies, to suggest the possible treatment way of COVID19 by focusing on the body's defense mechanism against pathogens.

Results: Antiviral drugs and immune-modulatory agents with the traditional medicines using the natural compound are usual accessible treatments. Accordingly, they have better beneficence due to the large existence studies, long time follow-ups, proximity to the natural system, and the normal physiological routine of the pathogen and host interactions. Besides, the serotonergic and dopaminergic pathways are considered as attractive targets to treat human immune, infectious, and cancerous diseases. Fluoxetine, as a host-targeted small molecule with immunomodulatory action, may be known as effective drug for treatment and prevention of COVID19 disease, in combination with antiviral drugs and natural compounds.

Conclusion: Co-administration of fluoxetine in the treatment of COVID19 could be considered due to the possibility of its interaction with ACE2 receptors, immune-modulatory function, and a proper immune response at the right time. Fluoxetine plays a beneficial role in reducing stress due to fear of infecting by COVID19 or worsening the disease and psychological support for the affected patients.

Keywords: COVID-19; clinical trials; fluoxetine; immunomodulatory; therapeutic drugs.

Figure 1

(A) The phylogenetic tree of SARS-like coronaviruses complete genome sequences. (B) The complete genome sequences of SARS-CoV, MERS-CoV, and SARS-CoV-2. Notes: Reprinted from Journal of Pharmaceutical Analysis, Vol 10/edition number 2, Li X, Geng M, Peng Y, Meng L, Lu S, Molecular immune pathogenesis and diagnosis of COVID-19, Pages No.102–108, Copyright (2020), with permission from Elsevier.

Figure 2

A vision of coronavirus with the minimal set of structural proteins. Notes: Reprinted from Advances in Virus Research, Vol 66, Masters PS, The molecular biology of coronaviruses, Pages No.193–292, Copyright (2006), with permission from Elsevier.9

Figure 3

Blocking of S1 Subunit and protease inhibition prevents the SARS-CoV-2 entry into target cell. Therefore S1 subunit and host proteases are potential therapeutic ways for the treatment of COVID-19. Notes: Reprinted from Archives of Medical Research, Vol 66, Arafah A, Ali S, Yatoo AM, Ali MN, Rehman MU, S1 subunit and  host proteases as potential therapeutic avenues for the treatment of COVID-19, In press, Copyright (2020), with permission from Elsevier.10

Figure 4

The RBM region of S proteins from SARS-CoV-2 and SARS-CoV alignment. Notes: (A) The six key amino acids in the S protein interacting with human ACE2 shown by black triangles. (B) Structural Alignment of the ACE2 recognition of RBD from SARS-CoV-2 and SARS-CoV. Human ACE2 (hACE2), SARS-CoV-2 RBD, and SARS-CoV RBD are in orange-red, blue, and green, respectively. Reprinted from Biochemical and Biophysical Research Communications, Vol 526/ Edition 1, Luan J, Lu Y, Jin X, Zhang L, Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection, Pages No.165–169, Copyright (2020), with permission from Elsevier.64

Figure 5

The interaction among nervous, endocrine, and immune systems, modulated by the secreted hormones, neurotransmitters, and cytokines. Notes: Reproduced from Szałach ŁP, Lisowska KA, Cubała WJ. The influence of antidepres-sants on the immune system. Arch Immunol Ther Exp (Warsz). 2019;67(3):143–151.86

Figure 6

The crosstalk effect of fluoxetine in intracellular signaling and its immune-regulatory role. Notes: Reprinted from Pharmacological Research, Vol 109, Di Rosso ME, Palumbo ML, Genaro AM, Immunomodulatory effects of fluoxetine: a new potential pharmacological action for a classic antidepressant drug?, Pages No.101–107, Copyright (2016), with permission from Elsevier.87