Former WTA world number one Serena Williams collected 10 of the last 12 games by lifting her level, to be sure.
Bopanna and Shapovalov will take on Dutch-Romanian combination of Jeal-Julien Rojer and Horia Tecau in the US Open quarters.
In the third-round clash, Serbian outclassed Struff in straight sets 6-3, 6-3, 6-1 in a match that lasted for one hour and 42 minutes.
In the first round clash, Bopanna and Shapovalov thrashed the American pair of Escobedo and Rubin in straight sets 6-2 6-4.
The former world number one was demolished by the 20-year-old Canadian 6-2, 6-3, 6-4 inside Arthur Ashe Stadium in 2hr 8min.
Playing against the second seeded Austrian, the Indian lost in straight sets to Thiem, who celebrated his 27th birthday with a commanding performance in the second round at the Athur Ashe stadium.
Sharan and Cacic lost 4-6 6-3 3-6 against Croatia's Mektic and Koolhof of the Netherlands in a tough contest that lasted one hour and 46 minutes on Wednesday.
World no 3 Pliskova ascended to the top spot in the draw -- and by Day 3, she was gone.
, Murray put together his 10th career comeback from two sets down and beat Yoshihito Nishioka 4-6, 4-6, 7-6 (5), 7-6 (4), 6-4.
Clijsters has been hampered this year by injuries, most recently an abdominal ailment that appeared to be an issue in the final set, when the pace of her serve dropped.
Serena and fellow American Kristie Ahn split the first 10 games before Williams pulled away to win 7-5, 6-3.
US Open: Sumit Nagal becomes first Indian since 2013 to enter second round of Grand Slam singles event
Nagal, who is the world number 122 will now face either Austria's Dominic Thiem or Spain's Jaume Munar in the second round of the US Open.
By the time the US Open fortnight is over, Osaka says she hopes to have honored the memory of six other victims of racial injustice.
Coco Gauff's hopes of launching another deep run at a Grand Slam ended in the first round at the US Open on Monday.
The No. 1-ranked Djokovic began his bid for Grand Slam title No. 18 on Monday night by extending his season start to 24-0 with a 6-1, 6-4, 6-1 victory over Damir Dzumhur at Flushing Meadows.