The antiviral protein cyanovirin-N: the current state of its production and applications

Abstract

HIV/AIDS continues to spread worldwide, and most of the HIV-infected people living in developing countries have little or no access to highly active antiretroviral therapy. The development of efficient and low-cost microbicides to prevent sexual transmission of HIV should be given high priority because there is no vaccine available yet. Cyanovirin-N (CVN)is an entry inhibitor of HIV and many other viruses, and it represents a new generation of microbicide that has specific and potent activity, a different mechanism of action and unusual chemicophysical stability. In vitro and in vivo antiviral tests suggested that the anti-HIV effect of CVN is stronger than a well-known gp120-targeted antibody (2G12) and another microbicide candidate, PRO2000. CVN is a cyanobacteria-derived protein that has special structural features, making the artificial production of this protein very difficult. In order to develop an efficient and relatively low cost approach for large scale production of recombinant CVN to satisfy medical use, this protein has been expressed in many systems by trial-and-error. Here, to summarize the potential, and remaining challenges, for the development of this protein into an HIV prevention agent, the progress in the structural mechanism determination, heterologous production, and pharmacological evaluation of CVN is reviewed.

Chimeric Cyanovirin-MPER Recombinantly Engineered Proteins Cause Cell-Free Virolysis of HIV-1

“…1A). CVN broadly inactivates HIV-1 and is a microbicidal candidate in its own right (16). CVN binds to carbohydrates on gp120, which, in the context of a trimeric spike, evidently prevents the binding of gp120 to CD4 (17) but does not induce poration of virus.…”

HIV sexual transmission and microbicides

“…Questions remain about the duration of colonisation and effectiveness against bacterial vaginosis [134]. Efforts are also put into bioengineering lactobacilli expressing proteins with specific antiviral properties such as interfering with HIV entry and fusion [135][136][137][138]. Despite the encouraging in vitro test results, the duration of colonisation and ensuring sufficiently high and prolonged expression and stability of the anti-HIV substance remain obstacles for further development.…”

Cyanobacterial lectins characteristics and their role as antiviral agents

“…A new generation of microbicide is represented by Cyanovirin-N owing to its specific and potent activity, unusual chemicophysical stability and different mechanism of action [58]. Anti-HIV activity of CV-N is stronger than other well known microbicide candidate, PRO2000 as revealed by in vitro and in vivo antiviral tests [59].…”

“…Anti-HIV activity of CV-N is stronger than other well known microbicide candidate, PRO2000 as revealed by in vitro and in vivo antiviral tests [59]. However, artificial production of this protein is difficult owing to its special structural features, thus for medical benefits it has been expressed in many systems using low cost approach for its large scale production [58].…”