Application of Nanotechnology in the COVID-19 Pandemic

Abstract

COVID-19, caused by SARS-CoV-2 infection, has been prevalent worldwide for almost a year. In early 2000, there was an outbreak of SARS-CoV, and in early 2010, a similar dissemination of infection by MERS-CoV occurred. However, no clear explanation for the spread of SARS-CoV-2 and a massive increase in the number of infections has yet been proposed. The best solution to overcome this pandemic is the development of suitable and effective vaccines and therapeutics. Fortunately, for SARS-CoV-2, the genome sequence and protein structure have been published in a short period, making research and development for prevention and treatment relatively easy. In addition, intranasal drug delivery has proven to be an effective method of administration for treating viral lung diseases. In recent years, nanotechnology-based drug delivery systems have been applied to intranasal drug delivery to overcome various limitations that occur during mucosal administration, and advances have been made to the stage where effective drug delivery is possible. This review describes the accumulated knowledge of the previous SARS-CoV and MERS-CoV infections and aims to help understand the newly emerged SARS-CoV-2 infection. Furthermore, it elucidates the achievements in developing COVID-19 vaccines and therapeutics to date through existing approaches. Finally, the applicable nanotechnology approach is described in detail, and vaccines and therapeutic drugs developed based on nanomedicine, which are currently undergoing clinical trials, have presented the potential to become innovative alternatives for overcoming COVID-19.

Keywords: COVID-19; SARS-CoV-2; antiviral drug; nanoparticles; nanotechnology; vaccines.

Figure 1

SARS-CoV, MERS-CoV, SARS-CoV-2 overview. (A) The origin of SARS-CoV, MERS-CoV and SARS-CoV-2 is widely known as bats as native hosts. While SARS-CoV and MERS-CoV have been shown to be intermediary hosts in civets and camels, SARS-CoV-2 can infect humans through an as-yet unknown intermediate host. After animal infection, SARS‐CoV‐2 has spread rapidly worldwide to date, mainly through continuous human-to-human transmission. (B) Schematic structure of SARS-CoV-2, MERS-CoV and SARS-CoV including Hemagglutinin Esterase, Membrane protein, RNA & Nucleocapsid protein, Envelope, and Spike protein. (C) Comparison of the S proteins of SARS-CoV, MERS-CoV and SARS-CoV-2. NTD, RBD, FP, HR and Cleavage site by TMPRSS2 and furin. (D) The MERS-CoV, SARS-CoV, and SARS-CoV-2 S proteins bind to ACE2 and DPP4, which act as receptors present in host cells. In order for the S2 domain in the virus to be fused to the host cell membrane to cause endocytosis, the process of cutting at two sites (S1/S2 and S2’) through the proteases Furin and TMPRSS2 is essential. SARS-CoV-2 has a much higher affinity than binding affinity to SARS-CoV S protein and ACE2, resulting in a high infection rate.

Figure 2

Global distribution of SARS-CoV-2 Clades (26 June 2020). The distribution of clades by continent (North America, South America, Europe, Africa, Asia, and Oceania) was plotted as a percentage and the major clades of each continent were indicated. Amino acid mutations are indicated for each clade, and the resulting changes in the function of SARS-CoV-2 are summarized using a table.

Figure 3

The SARS-CoV-2 life cycle and potential targets by antiviral agents as therapeutic strategies. (A) SARS-CoV-2 entry in target cell through endocytosis or interaction of S protein and ACE2. (B) Releasing SARS-CoV-2 genomic RNA. (C), (D) Viral polyproteins are translated and cleaved to form a replication transcription complex (RTC). (E) Genomic and subgenomic RNA replication. (F) Subgenomic RNAs produced through the transcription are translated into viral structural proteins inserted in endoplasmic reticulum (ER). (G) The viral nucleocapsid, assembled viral genomic RNA and structural proteins, bud into the lumen of the ER-Golgi intermediate cavity (ERGIC). (H) Exocytosis of SARS-CoV-2. 1. Antiviral drugs; chloroquine (CQ), hydroxychloroquine (HCQ), lopinavir/ritonavir (LPV/r), and remdesivir. 2. S protein and ACE2 interaction inhibitors; EK1 peptide. 3. Neutralizing antibodies; 47D11. 4. Immunotherapy (Anti-interleukin (IL)-6 Drugs); tocilizumab and sarilumab. 5. Convalescent plasma therapy; Convalescent plasma (CP).

Figure 4

Classical vaccine, modern vaccine and nanotechnology applied vaccine against SARS-CoV-2. Types of classic vaccines and representative candidate vaccines in clinical trials, Nanoparticles applicable to contemporary vaccines using DNA, RNA, and subunits, representative candidate vaccines in clinical trials, and mechanism of action of nanotechnology-based vaccines in APC.