The　ongoing　pandemic　of　coronavirus　disease　2019　(COVID-19)　posed　a　major　challenge　to　the　public　health.　Currently,　no　proven　antiviral　treatment　for　Severe　Acute　Respiratory　Syndrome　Coronavirus　2　(SARS-CoV-2)　infection　is　available.　Here　we　report　compounds　pentalysine　beta-carbonylphthalocyanine　zinc　(ZnPc5K)　and　chlorin　e6　(ce6)　potently　inhibited　the　viral　infection　and　replication　in　vitro　with　EC50　values　at　nanomolar　level.　These　compounds　were　first　identified　by　screening　a　panel　of　photosensitizers　for　photodynamic　viral　inactivation.　Such　viral　inactivation　strategy　is　implementable,　and　has　unique　advantages,　including　resistance　to　virus　mutations,　affordability　compared　to　the　monoclonal　antibodies,　and　lack　of　long-term　toxicity.