Coronavirus nsp13 contains a superfamily1 helicase domain linked to an N-terminal zinc-binding domain that is essential for helicase activity in vitro. The protein is able to unwind dsRNA and dsDNA in a 5′-to-3′ direction with the energy obtained by the hydrolysis of all NTPs and dNTPs. It was proposed that the resulting ssRNAs probably serve as templates for RNA synthesis by the RdRp. Besides NTPase and dNTPase activities, coronavirus helicases also possess RNA 5′-triphosphatase (RTPase) activity, which may be involved in viral mRNA capping. Obviously, the nsp13 5′-to-3′ helicase activity does not fit the expected 3′-to-5′ polarity required to separate secondary structures in the RNA template during negative-strand synthesis. Thus, cellular helicases may bind the RTC to assist coronavirus proteins in 3′-to-5′ unwinding.