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Review
. 2020 Apr 19;83:104327.
doi: 10.1016/j.meegid.2020.104327. Online ahead of print.

Recent Progress and Challenges in Drug Development Against COVID-19 Coronavirus (SARS-CoV-2) - An Update on the Status

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Free PMC article
Review

Recent Progress and Challenges in Drug Development Against COVID-19 Coronavirus (SARS-CoV-2) - An Update on the Status

Tarek Mohamed Abd El-Aziz et al. Infect Genet Evol. .
Free PMC article

Abstract

Coronaviruses are a large group of viruses known to cause illnesses that vary between the common cold and more severe diseases to include severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). A novel coronavirus was identified in December 2019 in Wuhan city, Hubei province, China. This virus represents a new strain that has not been previously identified in humans. The virus is now known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting disease is called coronavirus disease 2019 (COVID-19). The World Health Organization (WHO) declared the novel coronavirus outbreak a global pandemic in March 2020. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with more than 1,948,617 laboratory-confirmed cases and over 121,846 deaths worldwide. Currently, no specific medication is recommended to treat COVID-19 patients. However, governments and pharmaceutical companies are struggling to quickly find an effective drug to defeat the coronavirus. In the current review, we summarize the existing state of knowledge about COVID-19, available medications, and treatment options. Favilavir is an antiviral drug that is approved in Japan for common influenza treatment and is now approved to treat symptoms of COVID-19 in China. Moreover, Chloroquine and hydroxychloroquine, drugs used to treat malaria and arthritis, respectively, were recommended by the National Health Commission of the People's Republic of China for treatment of COVID-19. Presently, chloroquine and hydroxychloroquine are under investigation by the US Food and Drug Administration (FDA) as a treatment for COVID-19. The first COVID-19 vaccine is not expected to be ready for clinical trials before the end of the year.

Keywords: COVID-19; Coronavirus; Pathogenesis; SARS-CoV-2; Severe acute respiratory syndrome; Therapy; Vaccines.

Conflict of interest statement

Declaration of Competing Interest The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Structure of SARS-CoV-2. (A) Illustration of the SARS-CoV-2 virion created at the Centers for Disease Control and Prevention (CDC). The spikes on the outer edge of the virus particles look like a crown, giving the disease its characteristic name. (B) Schematic representation of the structure of SARS-CoV-2. It has four structural proteins, S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins; the N protein holds the RNA genome, and the S, E, and M proteins together create the viral envelope. (C) An electron microscopic image of a thin section of SARS-CoV-2 within the cytoplasm of an infected cell, showing the spherical particles and cross-sections through the viral nucleocapsid (Sohrabi et al., 2020).
Fig. 2
Fig. 2
The life cycle of SARS-CoV-2 in human lung cells. Coronavirus is most often transmitted by droplets while sneezing and coughing and its journey begins in the first days after infiltration from the upper respiratory tract. The spike proteins of SARS-CoV-2 binds to ACE2 receptors. The virion then releases RNA genome into the cell and translation of structural and non-structural proteins follows. ORF1a and ORF1ab are translated to produce pp1a and pp1ab polyproteins, which are cleaved by the proteases that are encoded by ORF1a to yield non-structural proteins. This is followed by assembly and budding into the lumen of the ERGIC. Virions are then released from the infected cell through exocytosis (Adnan Shereen et al., 2020). NSP, non-structural proteins; ACE2, Angiotensin-Converting Enzyme 2; Rough ER, Rough Endoplasmic Reticulum; ERGIC, Endoplasmic Reticulum Golgi Intermediate Compartment.
Fig. 3
Fig. 3
The key reservoir and potential interspecies transmission routes of SARS-CoV, MERS-CoV and SARS-CoV-2. The ingesting of infected animal as a source of food is the major cause of animal to human transmission of the virus and due to close contact with an infected person, the virus is further transmitted to healthy persons. However, there are no documented cases of direct bat-human transmission. Solid black arrow represents the confirmed transfer while the broken line denotes unknown intermediate host and suspected transmission.
Fig. 4
Fig. 4
The most common symptoms of COVID-19 according to the WHO.
Fig. 5
Fig. 5
Global confirmed COVID-19 cases and associated deaths from January 11 to April 14, 2020. Inserted Pie chart shows the distribution of confirmed cases in each continent.
Fig. 6
Fig. 6
Global COVID-19 outbreak map, April 14, 2020. US now has more COVID-19 cases than any other country.

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