Flanker Dan Lydiate has been released from the squad after suffering a serious knee injury in the 21-16 win over Ireland.
Centre Johnny Williams, wing Hallam Amos and scrum-half Tomos Williams will miss the match against Scotland.
Uncapped Halaholo was called up against Barbarians in November 2019.
The 30-year-old centre missed the non-capped international after suffering a serious knee injury playing for his region that ruled him out for almost a year.
New Zealand-born Halaholo qualified through residency after joining the Cardiff Blues in 2016.
Veteran British and Irish Lions centre Jamie Roberts has been in form for Dragons his season, but remains training with his region.
Player call-ups will be officially made and announced following the latest round of Covid-19 testing and results.
Wales coach Wayne Pivac is hoping George North will be fit for Scotland after the 28-year-old back suffered a scratched eye during the second half of his try-scoring performance on Sunday.
Dragons centre Nick Tompkins is also struggling with a shoulder injury, with Owen Watkin the other fit midfield man in the squad.
Scarlets centre Jonathan Davies will again be missing at Murrayfield having been unavailable to face Ireland with an ankle injury.
Tomos Williams is in danger of missing the rest of the tournament with the hamstring problem he suffered against Ireland.
His Cardiff Blues team-mate Lloyd Williams has been summoned ahead of Rhys Webb, whose pace and speed of pass was questioned by Pivac when the Six Nations squad was named in January.
Gareth Davies and Kieran Hardy are the other scrum-halves in the squad.
Lloyd Williams, 31, was called up to the autumn internationals squad after a four-year international absence and featured against Ireland, England and Scotland.
Cardiff Blues back-rower Botham was also brought into the autumn internationals squad as a replacement and won three caps against Georgia, England and Italy before being omitted from the Six Nations party.
Wing Josh Adams is also absent for Scotland as he serves the second game of a two-match ban after breaching Covid-19 regulations.
Liam Williams will be back after suspension after being sent off for Scarlets against Cardiff Blues last month and is in line to replace the concussed Amos.