By targeting the catalytic site of RdRp protein using a novel strategy of generating molecules and validation by rigorous free energy calculations using well-tempered metadynamics, we were able to get at least five molecules that can bind more strongly than RTP, indicating the success of our approach. The free energy landscape using the X and θ collective variables was able to provide key insights into the directionality of movement for each candidate in the unbinding process. It is found that the unbinding of the molecules happens through the small opening at the finger and thumb subregion of the RdRp protein. We found some repurpose drugs that show, in our free energy calculation, stronger binding than RTP. We show that starting with only the receptor, our approach can propose novel molecules and also repurpose drugs for binding to a receptor. Therefore, the present approach is a unique way to explore chemical space for drug design, while also capturing the known and readily useable repurpose drugs. The computational validation using all-atom, explicit water is expensive; however, reliable in terms of binding free energy prediction. The success rate from de novo score to the free energy stability could encourage one to try the method on other known receptors for lead generation. We, however, think that there is a huge scope of improvement. We need to consider protein flexibility and the inclusion of water along with better scoring function. Also, to directly use as a drug, we need to screen the binders for potential drug likeness and synthesizability. Work along those directions are under progress.