Aim: Virtual screening of deep-sea fungal metabolites against SARS-CoV-2 Delta and Omicron spikes as potential antivirals.Materials & methods: Deep-sea fungal alkaloids (n >= 150) were evaluated against SARS-CoV-2, Delta and Omicron spikes, using various in silico approaches, including Admet scores, physiochemical properties, molecular docking (MD) and MD simulation (150 ns).Results: The test alkaloids complied with Admet scores and physiochemical properties within acceptable ranges, and followed Lipinski's rule of five. Of these, Cladosporium sphaerospermum-derived cladosin K (tetramate alkaloid) for SARS-CoV-2, Cystobasidium laryngis-derived saphenol (phenazine alkaloid) for Delta and Chaetomium globosum-derived chaetoglobosin E (quinoline alkaloid) for Omicron were identified as potential spike-inhibitors.Conclusion: Our data therefore, strongly warrants further experimental validations of cladosin K, saphenol and chaetoglobosin E, especially against the Omicron and Delta spikes.