Why this sentence is not English?

But why is "Drug A makes the virus to resist to Drug B" so unpleasant?

It's unpleasant because it's ungrammatical.

It's the use of the infinitive "to resist." It doesn't indicate direct action.

Also, the second "to" in unnecessary.

The present subjunctive does indicate direct action: "Drug A makes the virus resist Drug B."

Why this sentence is not English?

Quote:

Why this sentence is not English?

That is a mistake, which should be "Why is this sentence not English?"

or maybe "I want to know why this sentence is not English."

I wonder why "Drug A makes the virus resist Drug B" can be without "to"(isn't "make..to (verb)" okay?)?

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I wonder why "Drug A makes the virus resist Drug B" can be without "to"(isn't "make..to (verb)" okay?)?

Drug A makes the virus resist drug B.

there, resist is a verb

Drug A makes the virus resistant to drug B.

there, resistant is an adjective, and "to" is required.

Ah, McTag, I meant that "Drug A makes the virus to resist drug B" is also okay.
Okay or not in your eye? Why and why not.

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Ah, McTag, I meant that "Drug A makes the virus to resist drug B" is also okay.
Okay or not in your eye? Why and why not.

Not okay.

It's not really wrong I suppose, but it sounds very awkward and not colloquial.

"causes the virus to resist" sounds right, and there is very little difference as you see.
But "makes the virus to resist" just sounds clunky.

Examples: Miss Jones felt compelled to resist his advances.

The scientist made a virus to resist the infection...that's okay, but has a slightly different meaning, "made" meaning "created" and not "compelled".