Here we report that unlike TRIM2, SIRPA has broad antiviral restriction activity in many different cell types and decreases infection by a variety of enveloped RNA viruses that require trafficking to an acidic compartment, including LCMV, VSV and the flavivirus Zika virus (ZIKV), as well as pseudotyped viruses bearing the glycoproteins of the coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Machupo virus (MACV) and the filovirus Ebola virus (EBOV). The gene discussed is SIRPA; the disease is infection.