SBPH—The Twitter thread you cited is quite technical. I get the issue of nucleoside phosphorylation (e.g. #msg-42396728, #msg-64569966, #msg-64570180); however, my understanding is that the second and third phosphorylation steps are not as finicky as the first, so I might not fully gree with John Tucker's tweets in the thread you referenced.
p.s. I plan to listen to the SBPH CC replay over the weekend.
“The efficient-market hypothesis may be the foremost piece of B.S. ever promulgated in any area of human knowledge!”