1  Introduction
The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) has spread to >210 countries, which is rare among acute infectious diseases in recent years, and caused a great threat to global public health [1]. This disease was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and it is the third documented spillover of an animal coronavirus to humans in only two decades [2,3]. Since the first human coronavirus detected in the 1960s, SARS-CoV-2 is the seventh coronavirus that is known to infect humans (Fig. 1 ) [4]. There are four types of coronaviruses named as α, β, γ and δ, which only α- and β-type contain human pathogenic strains [1,4]. SARS-CoV-2, including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), are all β-coronal viruses [3].
Fig. 1 The virus types and symptoms of 7 important pathogenic human coronaviruses.
Coronaviruses (CoVs) are enveloped single-stranded positive-sense RNA viruses (Fig. 2A), which widely infected vertebrates including humans and animals, to cause respiratory and enteric diseases [[5], [6], [7]]. Spike glycoprotein (S protein) plays a major role in the pathogenesis of coronavirus, inducing host immune responses, and is considered a primary target for vaccine preparation [1,8]. Current information indicates that SARS-CoV-2 is more contagious than SARS-CoV including person­to­person spread, which poses a serious threat to human health [3,9].
Fig. 2 The structure of CoV virion and S protein, (A) Depiction of the CoV virion; (B) Depiction of S protein. A single S protein is depicted as a rectangle, and relevant structural features are highlighted as follows: N-terminal receptor binding domain (N-RBD) in dark blue; C-RBD in brown; cleavage sites (CS) 1 and 2, fusion peptide (FP) in red, heptad repeat (HR) regions 1 and 2 in green; transmembrane span (TM) depicted as membrane bilayer; cytoplasmic tail (CT) in light blue.; (C) Structure of the MHV N-RBD in complex with its CEACAM receptor.; (D) Structure of the SARS C-RBD in complex with its ACE2 receptor.; (E) Structure of the post-fusion HR1-HR2 bundle [7].
At present, there are almost no specific drugs for coronavirus therapy. Researchers have been working to inhibit growth of the virus, but the virus may mutate and develop resistance to these therapies [1,10]. It is urgent for the international medical community to develop targeted, high-efficiency and low-toxic drugs to treat the coronavirus based on the structure and property of the coronavirus. Polysaccharides have been used in traditional Chinese herbal medicine for at least 500 years [11], and have advantages of wide sources, low toxicity, good biocompatibility, and immune regulation [12,13]. Some polysaccharides, such as carrageenan, chitosan, fucoidan, and astragalus polysaccharide (APS), have been reported to show strong antiviral activity [[14], [15], [16], [17]]. In particular, sulfated polysaccharides can interfere with the entry process of virus by blocking the positive charge of the pathogen surface receptors, to prevent them from binding to heparan sulfate proteoglycan (HSPGs) on the surface of host cell [18]. Thus, polysaccharides are attractive candidates for developing potential antiviral agents. Here, we summarized and analyzed the antiviral properties, mechanisms, and applications of some polysaccharides and their derivatives in the anti-virus field, aiming to provide a new approach to the development of drugs and vaccines for the treatment of coronavirus, especially for COVID-19.