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Review
. 2021 Jun 30:12:658519.
doi: 10.3389/fimmu.2021.658519. eCollection 2021.

Potential Therapeutic Targets and Vaccine Development for SARS-CoV-2/COVID-19 Pandemic Management: A Review on the Recent Update

Uttpal Anand  1 , Shweta Jakhmola  2 , Omkar Indari  2 , Hem Chandra Jha  2 , Zhe-Sheng Chen  3 , Vijay Tripathi  4 , José M Pérez de la Lastra  5
Affiliations
Review

Potential Therapeutic Targets and Vaccine Development for SARS-CoV-2/COVID-19 Pandemic Management: A Review on the Recent Update

Uttpal Anand et al. Front Immunol. .

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly pathogenic novel virus that has caused a massive pandemic called coronavirus disease 2019 (COVID-19) worldwide. Wuhan, a city in China became the epicenter of the outbreak of COVID-19 in December 2019. The disease was declared a pandemic globally by the World Health Organization (WHO) on 11 March 2020. SARS-CoV-2 is a beta CoV of the Coronaviridae family which usually causes respiratory symptoms that resemble common cold. Multiple countries have experienced multiple waves of the disease and scientific experts are consistently working to find answers to several unresolved questions, with the aim to find the most suitable ways to contain the virus. Furthermore, potential therapeutic strategies and vaccine development for COVID-19 management are also considered. Currently, substantial efforts have been made to develop successful and safe treatments and SARS-CoV-2 vaccines. Some vaccines, such as inactivated vaccines, nucleic acid-based, and vector-based vaccines, have entered phase 3 clinical trials. Additionally, diverse small molecule drugs, peptides and antibodies are being developed to treat COVID-19. We present here an overview of the virus interaction with the host and environment and anti-CoV therapeutic strategies; including vaccines and other methodologies, designed for prophylaxis and treatment of SARS-CoV-2 infection with the hope that this integrative analysis could help develop novel therapeutic approaches against COVID-19.

Keywords: COVID-19; antibodies; peptide; therapeutic targets; treatment; vaccine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Diagrammatic representation of the structure of respiratory syndrome causing human CoV.
Figure 2
Figure 2
Schematic representation of SARS-CoV-2 genomic sequence. UTR, Untranslated region; ORF, Open reading frame; S, Spike protein; E, Envelope protein; M, Membrane protein; N, Nucleocapsid protein.
Figure 3
Figure 3
Image showing a screenshot as of 27 March 2021 (9:27 AM) of a collective global map of COVID-19 cases by the Center for Systems Science and Engineering, Johns Hopkins University, United States (37). This database is updated constantly and can be viewed at https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6. On the left-hand side, region/country showing nine most infected COVID-19 cases (circled in yellow color), on the top left-hand side global infected cases are showing (circled in green color), and on the top right-hand side global deaths are showing (circled in blue color).
Figure 4
Figure 4
(A) Factors involved in SARS-CoV-2 transmission and (B) mechanism of SARS-CoV-2 entry into the host cell. The transmission of SARS-CoV-2 occurs through various direct and indirect routes. Environmental factors like temperature and humidity show the impact on the transmission. Once the virus enters inside the host, it enters into the cell through angiotensin-converting enzyme 2 (ACE-2). It can also use various other cell surface receptors like neuropilin-1 to facilitate the entry and infectivity. By the membrane fusion or endosomal pathway, the virus releases its genetic material inside the cytoplasm. The viral RNA then gets transcribed and translated into polypeptides. The polypeptides are cleaved to generate various structural and non-structural proteins (nsps). The nsps help in viral replication and transcription. The more viral RNA copies are produced through the replication. Meanwhile, the structural proteins like E, M, and S proteins get embedded in the endoplasmic reticulum (ER) membrane and transported to Golgi through ER-Golgi intermediate complex (ERGIC). The multiple numbers of new virions are then assembled and exocytosed of the cell to infect nearby cells.
Figure 5
Figure 5
Anti-coronavirus therapies can be based on targeting the virus or targeting the host immune system. Targeting the virus comprises inhibition of viral entry and fusion, targeting the endocytosis, neutralizing virus replication and blocking virus repackaging. Targeting host immune system comprises antibody therapy with plasma from recovered or convalescent patients and suppression of the excessive inflammatory response.
Figure 6
Figure 6
Antiviral activity of peptides. Peptides can directly prevent or inhibit the viral entry, viral fusion and or the assembly and viral release. Peptides can also neutralize viral replication by interacting with relevant proteins inside the cell. For example, blocking the active sites of functional non-structural viral proteins and/or interfering with the generation of nucleic acids directly or via associated proteins.
Figure 7
Figure 7
Share of the population fully vaccinated (have received all doses prescribed by the vaccination protocol) against COVID-19, May 10, 2021. Retrieved from: ‘https://covid-nma.com/dataviz/’ [Online Resource].
Figure 8
Figure 8
Approaches of vaccine development. Current anti-viral vaccine strategies can be divided into those that resemble the virus and molecular-based or targeted vaccines. The vaccines based on attenuated or inactivated virus, and virus like particles (VLPs) keep viral structures, and or main components, whereas molecular targeted vaccines are composed on recombinant subunit proteins, and/or nucleic acids, such as DNA or RNA. A complete list of vaccines in development for each platform can be found at https://www.covid-19vaccinetracker.org.
Figure 9
Figure 9
Countries where the Cominarty (Pfizer-BioNTech) vaccine is being used as of May 10, 2021. Source: Our World in Data (https://ourworldindata.org/).
Figure 10
Figure 10
Countries where the Moderna vaccine is being used as of May 10, 2021. Source: Our World in Data (https://ourworldindata.org/).
Figure 11
Figure 11
Countries where the Vaxzevria (Oxford-AstraZeneca) vaccine is being used as of May 10, 2021. Source: Our World in Data (https://ourworldindata.org/).
Figure 12
Figure 12
Countries where the Ad26.COV2. S-Jansen (Johnson&Johnson) vaccine is being used as of May 10, 2021. Source: Our World in Data (https://ourworldindata.org/).
Figure 13
Figure 13
Countries where the Sputnik V (Gamaleya) vaccine is being used as of May 10, 2021. Source: Our World in Data (https://ourworldindata.org/).
Figure 14
Figure 14
Countries where the CoronaVac (Sinovac) vaccine is being used as of May 10, 2021. Source: Our World in Data (https://ourworldindata.org/).
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