Rabies is acute encephalitis that continuously kills thousands of people annually. There is no clinical cure for rabies so far and its prevention is limited to sero-vaccinations based on standard WHO protocols. Certain compounds such as snake venoms contain active biological components with tendency toward acetylcholine receptors and ion channels at the cell surface. These compounds then are able to reduce aggregation of the virus in neuromuscular junction that may lead to inhibit the virus activity. In this study we worked on cytotoxicity and antiviral activity effects of Naja naja oxiana (Iranian Caspian cobra) snake venom components, on Rabies Lyssavirus (Rabies virus; RABV) infected mammalian cells. The concentration of 25 μg/ml F5 fraction separated by FPLC showed minor toxicity on BHK-21 cells by MTT test and high antiviral activity against infected cells by FAT assay. Further studies on F5 fractionation by HPLC showed that the proliferation of infected BHK-21 cells by rabies virus CVS-11 strain was decreased up to 80% by using 20 μg/ml P5 peak, after 48 h. We assume that P5-peptide (MW < 10 kDa) enters the cells through AChR receptors same as rabies virus without competition in binding to the cell receptors and is able to reduce the virus proliferation on post viral infection phase. This is the first report of the presence of an anti-rabies effect of Caspian cobra snake venom component. As per our results the P5 peak is a suitable candidate for further studies as a new agent to reduce CVS-11 rabies virus.