Immunogenicity of Different Forms of Middle East Respiratory Syndrome S Glycoprotein.

The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreaks. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~35.5%. Currently, there are no registered vaccines or means of therapeutic protection against MERS in the world. The MERS-CoV S glycoprotein plays the most important role in the viral life cycle (virus internalization). The S protein is an immunodominant antigen and the main target for neutralizing antibodies. In the present study, the immunogenicities of five different forms of the MERS-CoV S glycoprotein were compared: the full-length S glycoprotein, the full-length S glycoprotein with the transmembrane domain of the G glycoprotein of VSV (S-G), the receptor-binding domain (RBD) of the S glycoprotein, the membrane-fused RBD (the RBD fused with the transmembrane domain of the VSV G glycoprotein (RBD-G)), and the RBD fused with Fc of human IgG1 (RBD-Fc). Recombinant vectors based on human adenoviruses type 5 (rAd5) were used as delivery vehicles. Vaccination with all of the developed rAd5 vectors elicited a balanced Th1/Th2 response in mice. The most robust humoral immune response was induced after the animal had been vaccinated with the membrane-fused RBD (rAd5-RBD-G). Only immunization with membrane forms of the glycoprotein (rAd5-S, rAd5-S-G, and rAd5-RBD-G) elicited neutralizing antibodies among all vaccinated animals. The most significant cellular immune response was induced after vaccination of the animals with the full-length S (rAd5-S). These investigations suggest that the full-length S and the membrane form of the RBD (RBD-G) are the most promising vaccine candidates among all the studied forms of S glycoprotein.

Thalicosides A1-A3, minor cycloartane bisdesmosides from Thalictrum minus.

Three new cycloartane bisdesmosides, two of which are based on a new genin, were isolated from the above-ground parts of Thalictrum minus. Thalicosides A1-A3 (1-3) were characterized as 3-O-beta-D-galactopyranosyl-29-O-beta-D-glucopyranosyl-3beta,16beta++ +, 29-trihydroxy-22(S),25-epoxycycloartane (1); 3-O-alpha-L-arabinopyranosyl-29-O-beta-D-glucopyranosyl-3beta,1 6beta, 29,22(S)-tetrahydroxycycloart-24-ene (2); and 3-O-alpha-L-arabinopyranosyl-29-O-beta-D-glucopyranosyl-3beta,1 6beta, 29-trihydroxy-22(S),25-epoxycycloartane (3), respectively. The structural assignments of these new compounds were based on interpretation of spectroscopic data. Thalicoside A2 showed in vitro inhibition of the fungus Candida albicans and also activity against Staphylococcus aureus.

Squarroside C, a new cycloartene bisdesmoside from Thalictrum squarrosum.

Squarroside C (1), a new cycloartane 3,21-bisdesmoside, was isolated from the above-ground parts of Thalictrum squarrosum. The structure of 1 was established as 3-O-[O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranosyl]-21-O-be ta-D-glucopyranosyl-21(S),22(S),23(R),3beta,21alpha,22beta, 30-tetrahydroxy-21,23-epoxycycloart-24-ene by 2D NMR spectroscopy and FABMS.

The elucidation of the structure of thalicoside F, A. minor oleanane glycoside from Thalictrum minus L.

A new triterpenoid saponin, thalicoside F was isolated from the above-ground part of Thalictrum minus L. (Ranunculaceae family) collected in Eastern Siberia (Russia). The structure of thalicoside F was elucidated by a combination of 1D- and 2D-NMR spectroscopy and mass spectroscopy, and was determined to be C47H74O17{3-beta-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D- glucopyranosyl-(1-->4)-alpha-L-arabinopyranosyl]-11 alpha, 12 alpha-epoxyoleanane-28,13 beta-olide}.