Introduction Acute gastroenteritis (diarrhea and vomiting) leads to 1.45 million deaths worldwide every year and is considered one of the greatest burdens of all infectious diseases, second only to respiratory infections. 1 Acute gastroenteritis can be caused by bacteria or viruses; the main viral pathogens of acute gastroenteritis are rotaviruses and Noroviruses (NoVs). Since the implementation of rotavirus vaccines in many countries, NoVs have replaced rotaviruses as the main etiologic agent of viral epidemic gastroenteritis. 2 They impose staggering economic costs and social burdens. 3 To date, there is no sufficient therapy or commercial vaccine for NoVs. 4 Viral Particle Structure and Function NoV was first discovered using electron microscopy (EM). It is a small, round (27-38 nm in diameter), non-enveloped, icosahedral virus belonging to the family Caliciviradae under the genus Norovirus. The NoV genome consists of a single positive-sense RNA which is approximately 7.5-7.7 kb and encodes three open reading frames (ORFs) 5 with the exception of the murine norovirus (MNV). MNV has a fourth alternative ORF. 6 The first ORF (ORF1) encodes a large nonstructural polyprotein which is post-translationally cleaved by a virus-encoded protease (Pro; NS6) into six or seven mature nonstructural proteins involved in viral replication 7 from the N to the C terminus including N-terminal protein (designated p48 for Norwalk virus; NS1-2), NTPase (p41; NS3), 3A-like protein (designated p22 for Norwalk virus; NS4), a viral genome-linked protein (VPg; NS5), viral protease (3Clpro; NS6), 8 and RNA-dependent RNA polymerase (RdRp; NS7). 9 The ORF2 and ORF3 encode the major capsid protein VP1 and the minor structure protein VP2, respectively. The icosahedral T3 recombinant NoV is formed by assembly of the 90 dimers of the VP1 capsid protein. VP1 is 1.8 kb in length and organized into two principal domains, the shell (S) and protrusion (P) domains. The S domain is highly conserved, which is related to the formation of the NoV's structure. The P domain can form virus-like particles, even with 20 aa missing in the N terminal, and still have no effect on the ability to function as a receptor. 10 The P domain is further subdivided into the P1 and P2 subdomains. The moderately flexible P1 sub-domain acts as a hinge to combine S and P2 sub-domains. The P2 sub-domain is located on the most distal surface and is highly variable. It http://ijtmgh.com